The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
What's new in allergy and immunology

Disclosures: Anna M Feldweg, MD Employee of UpToDate, Inc. Elizabeth TePas, MD, MS Employee of UpToDate, Inc.

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: Oct 2014. | This topic last updated: Nov 03, 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.

ASTHMA AND COPD

Aspirin therapy for aspirin-exacerbated respiratory disease (October 2014)

Aspirin desensitization followed by daily aspirin therapy is used in the treatment of aspirin-exacerbated respiratory disease (AERD). The utility of aspirin therapy in patients who have asthma and chronic polypoid rhinosinusitis but who tolerate aspirin has been unclear. In a small trial, 20 patients with AERD and 14 patients with asthma and CRS with nasal polyposis, but without aspirin intolerance, were randomized to receive aspirin therapy or placebo [1]. Aspirin therapy improved several asthma and rhinitis outcomes and led to lower maintenance doses of inhaled glucocorticoids in patients with aspirin intolerance, but was not beneficial in patients without aspirin intolerance. Although small, the findings of this trial support the clinical impression that aspirin's benefits are limited to patients with intolerance. (See "Aspirin-exacerbated respiratory disease: NSAID challenge and desensitization", section on 'Efficacy of aspirin therapy in AERD'.)

Mepolizumab for severe asthma associated with peripheral blood eosinophilia (October 2014)

The anti-interleukin-5 monoclonal antibody mepolizumab has previously been shown to reduce exacerbations in patients with severe asthma and eosinophilic airway inflammation. Two additional trials validate using peripheral blood eosinophil counts to select patients with severe asthma who are likely to respond to mepolizumab, demonstrate comparable effects of intravenous and subcutaneous preparations, and show a glucocorticoid-sparing effect.

The larger multicenter trial (MEpolizumab as adjunctive therapy iN patients with Severe Asthma, MENSA) evaluated mepolizumab (given either intravenously or subcutaneously every four weeks) in patients with severe asthma and eosinophilic airway inflammation despite high-dose inhaled glucocorticoids [2]. At 32 weeks, exacerbations were reduced by approximately 50 percent for the groups using mepolizumab given by either route, compared with placebo.

●   In a group of patients with severe asthma requiring systemic glucocorticoids, the SteroId ReductIon with mepolizUmab Study (SIRIUS) compared subcutaneous mepolizumab, given every four weeks, with placebo [3]. At 20 weeks, mepolizumab allowed a median reduction in the systemic glucocorticoid dose of 50 percent, decreased the number of asthma exacerbations, and improved control of asthma symptoms.

Mepolizumab is not commercially available at present, although it is under review by regulatory agencies. (See "Alternative and experimental agents for the treatment of asthma", section on 'Anti-IL-5 antibodies'.)

Intermittent montelukast for acute wheezing episodes in young children (September 2014)

Several randomized trials have examined the intermittent use of leukotriene receptor antagonists (LTRAs) in preschool children with recurrent wheezing, with mixed results. The most recent trial adds to the data that do not favor this approach in most children, although specific subgroups based upon genotype may benefit. In this trial, over 1300 children aged 10 months to 5 years with a history of two or more wheezing episodes were randomly assigned to intermittent montelukast or placebo at the onset of any subsequent wheezing episode over a 12 month period [4]. No difference between the groups was seen in the frequency of unscheduled medical visits for wheezing episodes, although subgroup analysis suggested the response to montelukast was modified by arachidonate 5-lipoxygenase (ALOX5) genotype. Further study is needed to define and confirm these subpopulations. (See "Treatment of recurrent virus-induced wheezing in young children", section on 'Intermittent leukotriene-receptor antagonists'.)

Clusters of enterovirus D68 infections in the United States (September 2014)

Since August 2014, clusters of severe respiratory infections due to enterovirus D68 have been reported across the continental United States [5,6]. These have occurred predominantly in children with a prior history of asthma and have been generally characterized by low grade or absent fever with wheezing, dyspnea, hypoxia, and perihilar infiltrates. Infection has also been associated with rare cases of limb weakness with spinal cord lesions on imaging. The possibility of enterovirus D68 should thus be suspected in cases of severe respiratory illnesses without alternative explanation, particularly in young children. Treatment is supportive and prevention relies on basic hygienic measures, including handwashing with soap and water. Alcohol-based sanitizers may be ineffective against enteroviruses. Enterovirus D68 had previously been implicated in smaller clusters of respiratory infections but was otherwise rarely reported. Additional surveillance information can be found on the CDC website. (See "Virus-induced wheezing and asthma: An overview", section on 'Enterovirus D68 infection' and "Clinical manifestations and diagnosis of enterovirus and parechovirus infections", section on 'Respiratory disease' and "Epidemiology, pathogenesis, treatment, and prevention of enterovirus and parechovirus infections", section on 'Serotypes and disease'.)

Long-acting beta agonist olodaterol for use in COPD (August 2014)

Olodaterol, a once-daily, long-acting beta agonist (LABA), is approved for the treatment of COPD in the United States, Canada, Russia, Denmark, and several other countries; it is not approved for use in asthma. In two trials that included a total of 1838 subjects with moderate-to-severe COPD, 24 weeks of olodaterol resulted in significant improvement in airflow limitation and quality of life, compared with placebo [7]. Similar results were seen in a separate pair of trials that included a total of 1266 subjects and lasted 48 weeks [8]. In all reports, adverse events with olodaterol were comparable to those of placebo. (See "Management of stable chronic obstructive pulmonary disease", section on 'Beta agonists'.)

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 [9]. 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 [10]. 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 [11]. 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 [12]. 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 [13]. 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'.)

DRUG HYPERSENSITIVITY

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 [14]. (See "Overview 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 [15]. 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'.)

FOOD ALLERGY AND INTOLERANCE

Infant feeding practices and risk of celiac disease (October 2014)

In the past, epidemiologic studies suggested that an infant's risk for developing celiac disease might be reduced by introducing gluten gradually between four and six months of age, ideally while breast feeding. This hypothesis was not confirmed by two new randomized trials, which found no association between the timing and manner of gluten introduction and celiac disease risk. One study included 944 infants in eight European countries who were at high risk for celiac disease because of their genetic profile. The infants were randomized to receive a small amount of gluten daily from 16 to 24 weeks of age, versus placebo [16]. There was no difference in celiac disease prevalence at three years of age, and the prevalence did not vary with exposure to breast feeding. A second study included 832 infants from Italy with high risk for celiac disease who were randomized to dietary introduction of gluten at six months of age versus 12 months of age [17]. Early introduction of gluten was associated with higher risk for celiac autoimmunity and overt celiac disease at two years of age, but there was no difference between the groups by five years of age, and no association with breast feeding was found. (See "Clinical manifestations and diagnosis of celiac disease in children", section on 'Infant feeding practices'.)

IMMUNODEFICIENCY

CTLA-4 haploinsufficiency with autoimmune infiltration (CHAI) disease (October 2014)

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an inhibitory receptor expressed on regulatory T (Treg) cells. Based on studies of four unrelated families, haploinsufficiency of CTLA-4 has been shown to result in an autoimmune lymphoproliferative syndrome (ALPS)-like disorder with dysregulation of Treg cells and hyperactivation of effector T cells. Patients demonstrated lymphoproliferation, lymphocytic infiltration of nonlymphoid organs, autoimmune cytopenias, and B cell abnormalities with hypogammaglobulinemia [18]. A similar spectrum of clinical complications can result from CTLA-4-blocking agents (eg, ipilimumab, abatacept) that are used in patients with cancer and autoimmune disease. (See "Autoimmune lymphoproliferative syndrome (ALPS): Clinical features and diagnosis", section on 'CTLA-4 haploinsufficiency with autoimmune infiltration (CHAI) disease'.)

Modified retrovirus vector for X-linked SCID gene therapy (October 2014)

Gene therapy is an effective treatment for primary immunodeficiencies such as X-linked severe combined immunodeficiency (SCID). However, it is associated with leukemia due to retroviral vectors preferentially integrating into proto-oncogenes. A self-inactivating retrovirus vector, in which the long terminal repeats containing viral enhancer sequences have been deleted, is under study for the treatment of X-linked SCID [19]. Seven of nine infants have been successfully treated using this vector, with decreased clustering of insertion sites within lymphoid proto-oncogenes and no reported cases of leukemia during the median 29.1 months of follow-up. Longer-term follow-up is necessary to confirm lack of leukemogenesis with this modified vector. (See "Gene therapy for primary immunodeficiency", section on 'X-linked SCID'.)

Inheritance patterns in hemophagocytic lymphohistiocytosis (August 2014)

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome of excessive immune activation seen in patients of all ages, predominantly infants and children. Gene mutations affecting cytotoxic lymphocyte function are often found. Genetic testing in a series of 2701 patients has now revealed a previously unappreciated mode of inheritance in HLH. In addition to homozygosity or compound heterozygosity for mutations in a single HLH gene, the disease can also be caused by digenic inheritance, in which separate mutations in two different HLH genes are found [20]. The specific genes involved appear to affect the age of disease onset. (See "Clinical features and diagnosis of hemophagocytic lymphohistiocytosis", section on 'Genetics'.)

Donor source and transplantation outcomes for severe combined immunodeficiency (August 2014)

Historically, HLA-matched related donors have been the preferred donor source for hematopoietic cell transplantation (HCT) in patients with severe combined immunodeficiency (SCID) and other primary immunodeficiencies, but most patients do not have such a donor available. Results from a series of 240 infants with SCID who had undergone HCT show that excellent survival is possible with any donor type if the transplantation occurs in the first 3.5 months of life and before the onset of infection [21]. Survival at 5 years was high regardless of donor type among infants transplanted at ≤3.5 months of age (94 percent) and among older infants who had not yet developed infection (90 percent) or whose infections had resolved (80 percent). (See "Hematopoietic cell transplantation for primary immunodeficiency", section on 'Early identification' and "Hematopoietic cell transplantation for primary immunodeficiency", section on 'Donor source'.)

RHINITIS AND RHINOSINUSITIS

Effect of intranasal fluticasone furoate on growth in children (August 2014)

Intranasal glucocorticoid sprays are the most effective single therapy available for allergic rhinitis, but are associated with a potential for systemic absorption that is of particular concern in growing children. Most previous studies were reassuring in this regard. However, in the largest trial to date, maximum dose intranasal fluticasone furoate resulted in a slight reduction in growth velocity in prepubescent children [22]. In this trial, more than 400 children ages 5.0 to 8.5 years at study entry with perennial allergic rhinitis were randomized to receive fluticasone furoate or placebo for 52 weeks, which resulted in a reduction in growth velocity of -0.27 cm/year (95% CI, -0.48 to -0.06 cm/year). There was no evidence of adrenal suppression. Of note, the protocol in this study did not allow for dose reduction once symptoms were controlled, which is often recommended when using these agents. Thus, a very small reduction in growth velocity is possible with some intranasal glucocorticoids, and dosing should be adjusted downward to the lowest effective dose that maintains symptom control. (See "Pharmacotherapy of allergic rhinitis", section on 'Safety in children and adults'.)

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'.)

URTICARIA AND ANGIOEDEMA

Recombinant C1 inhibitor for hereditary angioedema (August 2014)

Recombinant human C1-esterase inhibitor (conestat alfa) has been approved by the US Food and Drug Administration for treatment of acute attacks of hereditary angioedema in adolescents and adults [24]. This agent has been available in some other countries since 2011. It is collected from the milk of transgenic rabbits, and all patients should be screened for allergy to rabbit before receiving this agent, because severe allergic reactions have been reported in patients with pre-existing rabbit allergy. Studies directly comparing recombinant to plasma-derived C1 esterase inhibitor are lacking, although available data suggest that they are similarly effective. The recombinant product has a shorter half-life, requiring higher doses to achieve adequate plasma levels. (See "Hereditary angioedema: Treatment of acute attacks", section on 'Efficacy and adverse effects'.)

VACCINES AND VACCINE HYPERSENSITIVITY

Pneumococcal conjugate vaccine in adults ≥65 years of age (September 2014)

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 the pneumococcal conjugate vaccine (PCV13) for all adults ≥65 years of age [25]. 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.

The ACIP revision was prompted by results from the CAPiTA trial. This randomized placebo-controlled trial, including approximately 85,000 adults ≥65 years of age in the Netherlands, demonstrated the efficacy of PCV13 against vaccine-type pneumococcal pneumonia, vaccine-type nonbacteremic pneumococcal pneumonia, and vaccine-type invasive pneumococcal disease [26]. 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 'Indications'.)

ACIP recommendations for the 2014-2015 influenza season (August 2014)

In August 2014 the United States Advisory Committee on Immunization Practices (ACIP) released updated recommendations for the prevention of seasonal influenza with vaccines [27]. Important changes from previous recommendations include:

A preferential recommendation for the nasal spray vaccine (live attenuated influenza vaccine, LAIV) over the intramuscular injection (inactivated influenza vaccine, IIV) for children two through eight years of age who do not have specific contraindications to the nasal vaccine (eg, asthma, egg allergy, diabetes, immunosuppression). UpToDate agrees with this recommendation, but also prefers LAIV for children older than eight years. If LAIV is not immediately available, IIV should be administered to avoid missing an opportunity for influenza immunization. (See "Seasonal influenza in children: Prevention with vaccines", section on 'LAIV compared with IIV'.)

Changes to the dosing schedule for children six months through eight years of age (algorithm 2). (See "Seasonal influenza in children: Prevention with vaccines", section on 'Schedule'.)

Recommendations for adults are largely unchanged. (See "Seasonal influenza vaccination in adults", section on 'Overview'.)

Efficacy of high-dose influenza vaccine in elderly adults (August 2014)

Due to concern that standard-dose influenza vaccines may be less effective in elderly adults than in younger adults, a high-dose influenza vaccine, Fluzone high-dose, has been developed. In a trial that included more than 30,000 adults ≥65 years of age, Fluzone high-dose was modestly more effective than standard-dose Fluzone [28]. Among individuals in the high-dose group, 1.4 percent had laboratory-confirmed influenza associated with an influenza-like illness compared with 1.9 percent in the standard-dose group (relative efficacy 24.2 percent). The rates of serious adverse events were similar with the high-dose and standard-dose vaccines. For individuals ≥65 years of age, we prefer Fluzone high-dose when available rather than a standard-dose inactivated vaccine. However, the United States Advisory Committee on Immunization Practices has not stated a preference for Fluzone high-dose over the standard-dose inactivated influenza vaccine in older adults [27,29]. (See "Seasonal influenza vaccination in adults", section on 'High-dose vaccine' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation'.)

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. In August 2014, the US Food and Drug Administration (FDA) approved an intramuscular inactivated influenza vaccine (Afluria) for use with a jet injector device (PharmaJet Stratis needle-free injection system) for adults between 18 and 64 years of age [30]. The jet injector 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'.)

OTHER GENERAL ALLERGY AND IMMUNOLOGY

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) [32,33]. 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'.)

Hematopoietic stem cell transplant for advanced systemic mastocytosis (October 2014)

Some advanced forms of systemic mastocytosis (SM), specifically SM with an associated hematologic nonmast cell lineage disorder (SM-AHNMD), mast cell leukemia (MCL), and aggressive systemic mastocytosis (ASM), have carried poor prognoses. However, allogeneic hematopoietic cell transplant (allo-HCT) has been performed with increasing frequency for these disorders. The largest series to date evaluated outcomes of 57 patients who were treated with allo-HCT, using different types of donors and conditioning regimens [34]. Overall, 70 percent of patients responded, and nearly one-third demonstrated complete remission. Survival at three years was 74, 43, and 17 percent for SM-AHNMD, ASM, and MCL, respectively, which was significantly greater than historical controls, particularly for patients with SM-AHNMD. Myeloablative conditioning regimes were superior to reduced intensity regimens. Thus, these preliminary results are encouraging and further prospective trials are needed. HCT is not appropriate for indolent or cutaneous forms of SM. (See "Treatment and prognosis of systemic mastocytosis", section on 'Hematopoietic cell transplantation'.)

STING-associated vasculopathy with onset in infancy (August 2014)

Autoinflammatory diseases are due to pathogenic inflammation that arises through aberrant, antigen-independent activation of the immune system. A new autoinflammatory disease in children, stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI), has been identified [35]. SAVI is caused by gain-of-function mutations in the gene encoding STING (TMEM173, transmembrane protein 173). Patients present in early infancy with tachypnea and/or rashes (telangiectasia, pustules, and/or blisters) and develop marked vascular inflammation limited to the capillaries. Most patients also have recurrent low-grade fevers. Patients have not responded to the usual drugs used to treat rheumatologic disease, but blockade of interferon signaling is a potential therapeutic strategy. (See "Periodic fever syndromes and other autoinflammatory diseases: An overview", section on 'Chronic recurrent multifocal osteomyelitis'.)

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 [36]. 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'.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

  1. Swierczyńska-Krępa M, Sanak M, Bochenek G, et al. Aspirin desensitization in patients with aspirin-induced and aspirin-tolerant asthma: A double-blind study. J Allergy Clin Immunol 2014; 134:883.
  2. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014; 371:1198.
  3. Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014; 371:1189.
  4. Nwokoro C, Pandya H, Turner S. Intermittent montelukast in children aged 10 months to 5 years with wheeze (WAIT trial): a multicentre, randomised, placebo-controlled trial. Lancet Respir Med 2014.
  5. Missouri Department of Health and Senior Services. Health alert: Respiratory illnesses due to enterovirus D68 (EV-D68) in Missouri. August 29, 2014. http://health.mo.gov/emergencies/ert/alertsadvisories/pdf/HA82914.pdf (Accessed on September 12, 2014).
  6. Midgley CM, Jackson MA, Selvarangan R, et al. Severe respiratory illness associated with enterovirus D68 - Missouri and Illinois, 2014. MMWR Morb Mortal Wkly Rep 2014; 63:798.
  7. Koch A, Pizzichini E, Hamilton A, et al. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat® versus placebo and formoterol twice daily in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis 2014; 9:697.
  8. Ferguson GT, Feldman GJ, Hofbauer P, et al. Efficacy and safety of olodaterol once daily delivered via Respimat® in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis 2014; 9:629.
  9. Lynch SV, Wood RA, Boushey H, et al. Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children. J Allergy Clin Immunol 2014; 134:593.
  10. Gauvreau GM, O'Byrne PM, Boulet LP, et al. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N Engl J Med 2014; 370:2102.
  11. Been JV, Nurmatov UB, Cox B, et al. Effect of smoke-free legislation on perinatal and child health: a systematic review and meta-analysis. Lancet 2014; 383:1549.
  12. Criner GJ, Connett JE, Aaron SD, et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med 2014; 370:2201.
  13. Dogaru CM, Nyffenegger D, Pescatore AM, et al. Breastfeeding and childhood asthma: systematic review and meta-analysis. Am J Epidemiol 2014; 179:1153.
  14. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021014s035,021285s030lbl.pdf.
  15. Finkelstein Y, Macdonald EM, Li P, et al. Recurrence and mortality following severe cutaneous adverse reactions. JAMA 2014; 311:2231.
  16. Vriezinga SL, Auricchio R, Bravi E, et al. Randomized feeding intervention in infants at high risk for celiac disease. N Engl J Med 2014; 371:1304.
  17. Lionetti E, Castellaneta S, Francavilla R, et al. Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med 2014; 371:1295.
  18. Kuehn HS, Ouyang W, Lo B, et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 2014; 345:1623.
  19. Hacein-Bey-Abina S, Pai SY, Gaspar HB, et al. A modified γ-retrovirus vector for X-linked severe combined immunodeficiency. N Engl J Med 2014; 371:1407.
  20. Zhang K, Chandrakasan S, Chapman H, et al. Synergistic defects of different molecules in the cytotoxic pathway lead to clinical familial hemophagocytic lymphohistiocytosis. Blood 2014; 124:1331.
  21. Pai SY, Logan BR, Griffith LM, et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med 2014; 371:434.
  22. Lee LA, Sterling R, Máspero J, et al. Growth velocity reduced with once-daily fluticasone furoate nasal spray in prepubescent children with perennial allergic rhinitis. J Allergy Clin Immunol Pract 2014; 2:421.
  23. Patel A, deShazo RD, Stringer S. Diagnostic criteria for a curable form of chronic rhinosinusitis: the mucous recirculation syndrome. Am J Med 2014; 127:586.
  24. US Food and Drug Administration letter of approval. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm405526.htm (Accessed on July 21, 2014).
  25. Tomczyk S, Bennett NM, Stoecker C, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2014; 63:822.
  26. Bonten M, Bolkenbaas M, Huijts S, et al. Community acquired pneumonia immunization trial in adults (CAPiTA). Abstract no. 0541. Pneumonia 2014; 3:95. https://pneumonia.org.au/public/journals/22/PublicFolder/ABSTRACTBOOKMASTERforwebupdated20-3-14.pdf (Accessed on September 19, 2014).
  27. Grohskopf LA, Olsen SJ, Sokolow LZ, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP) -- United States, 2014-15 influenza season. MMWR Morb Mortal Wkly Rep 2014; 63:691.
  28. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med 2014; 371:635.
  29. Centers for Disease Control and Prevention (CDC). Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices--United States, 2013-2014. MMWR Recomm Rep 2013; 62:1.
  30. US Food and Drug Administration. FDA updated communication on use of jet Injectors with inactivated influenza vaccines. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/QuestionsaboutVaccines/ucm276773 (Accessed on August 21, 2014).
  31. McAllister L, Anderson J, Werth K, et al. Needle-free jet injection for administration of influenza vaccine: a randomised non-inferiority trial. Lancet 2014; 384:674.
  32. Simpson EL, Chalmers JR, Hanifin JM, et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol 2014; 134:818.
  33. Horimukai K, Morita K, Narita M, et al. Application of moisturizer to neonates prevents development of atopic dermatitis. J Allergy Clin Immunol 2014; 134:824.
  34. Ustun C, Reiter A, Scott BL, et al. Hematopoietic stem-cell transplantation for advanced systemic mastocytosis. J Clin Oncol 2014; 32:3264.
  35. Liu Y, Jesus AA, Marrero B, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med 2014; 371:507.
  36. Beck LA, Thaçi D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 2014; 371:130.
Topic 8363 Version 3983.0

Topic Outline

GRAPHICS

RELATED TOPICS

All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.