The following represent additions to UpToDate since the last version of What’s New that were considered by the authors and editors to be of particular interest.
ASTHMA
Long-acting beta agonists — The safety of long-acting beta agonists (LABAs) in asthma was examined in the most extensive meta-analysis to date, performed by the US Food and Drug Administration. An increased risk of serious asthma events (hospitalization, intubation, or death) was associated with LABA therapy in the overall population (60,954 patients), particularly among the youngest patients aged 4 to 11 years [1]. However, this increased risk was not seen in children and adolescents who also received inhaled glucocorticoids as an assigned study treatment. Conclusions regarding the protective effect of inhaled glucocorticoids are limited by the small number of patient events in this subgroup. (See "Beta agonists in asthma: Controversy regarding chronic use", section on 'Meta-analysis and clinical trial data'.)
Intermittent high dose inhaled glucocorticoids in young children — Intermittent high dose inhaled budesonide (1 mg twice daily for seven days, started early in the course of an upper respiratory tract infection) was compared with standard daily dose inhaled budesonide (0.5 mg nightly) in a randomized trial of 278 children aged 12 to 53 months with recurrent wheezing [2]. Intermittent high dose budesonide was as effective as daily standard dose therapy for multiple measures, including need for rescue therapy with oral glucocorticoids and bronchodilators, episode-free days, and symptom severity during respiratory illnesses. Previous randomized trials of intermittent high dose inhaled glucocorticoids compared with placebo have had mixed results. Intermittent standard dose inhaled glucocorticoids does not appear to be effective in this population, particularly when started after the onset of lower respiratory tract symptoms. (See "Treatment of virus-induced wheezing in young children", section on 'Intermittent inhaled glucocorticoids'.)
Proton pump inhibitor therapy in poorly controlled asthma — In a randomized trial, 306 children with poorly controlled asthma, but without symptoms of gastroesophageal reflux (GER), were randomly assigned to lansoprazole (weight-based dosing) or placebo for 24 weeks [3]. No differences in the asthma control questionnaire (ACQ) scores or lung function were noted between treatment groups. In a subset of 115 children with pH probe monitoring results, 49 (43 percent) had evidence of acidic reflux. No difference in asthma outcomes was noted in this subgroup, although the number of patients was small. Proton pump inhibitor therapy does not improve asthma outcomes in patients with poorly controlled asthma who do not have symptoms of GER. (See "Gastroesophageal reflux and asthma", section on 'Asymptomatic patients'.)
Anti-interleukin-5 antibody — The safety and efficacy of the monoclonal anti-interleukin (IL)-5 antibody was assessed in a randomized trial of 106 patients with poorly-controlled eosinophilic asthma. Subjects received intravenous infusions of reslizumab or placebo for 12 weeks [4]. The reslizumab group had a greater reduction in sputum eosinophils and improved airflow obstruction, but only a trend toward improved asthma control as measured by the Asthma Control Questionnaire (ACQ). (See "Alternative and experimental agents for the treatment of asthma", section on 'Anti-IL-5 antibodies'.)
ATOPIC DERMATITIS (ECZEMA)
Breastfeeding not protective against the development of eczema — In the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two study, the association between breastfeeding and eczema was examined in over 50,000 children aged 8 to 12 years from both high and low income countries [5]. A slight significant increased risk of ever having eczema was found in children ever breastfed; when the duration of breastfeeding was taken into account, a small increased risk was found for children who had been breastfed <6 months, but no association was noted in children breastfed for ≥6 months. Allergen sensitization and parental atopy did not modify these results. These results are consistent with a 2009 meta-analysis of studies that were performed almost exclusively in developed, high income countries. (See "The impact of breastfeeding on the development of allergic disease", section on 'Breastfeeding and atopic dermatitis (eczema)'.)
COPD
Vitamin D and COPD exacerbations — High dose vitamin D supplementation did not reduce the incidence of exacerbations in patients with moderate to very severe COPD who were randomly assigned to take vitamin D 100,000 IU or placebo orally every four weeks for a year [6]. The median time to first exacerbation did not differ between the groups, nor did exacerbation rates, FEV1, hospitalization, quality of life, or death. However, the rate of exacerbations was reduced in patients with severe vitamin D deficiency (serum 25-[OH] D levels <10 ng/mL) at baseline. Further research is needed to validate this latter observation. (See "Management of acute exacerbations of chronic obstructive pulmonary disease", section on 'Prevention'.)
DRUG HYPERSENSITIVITY
Clopidogrel hypersensitivity reactions — Hypersensitivity reactions develop in 1 to 4 percent of patients who receive clopidogrel following a coronary artery stenting procedure. Management options include stopping clopidogrel and changing to another antiplatelet agent, restarting the clopidogrel using a desensitization procedure, or continuing the drug while treating the patient with systemic glucocorticoids and antihistamines (ie, “treating through”). An observational study reported outcomes for a series of 62 patients with mild to moderate clopidogrel reactions who were managed by “treating through” and also evaluated with various allergy tests to define the nature of their reactions [7]. Hypersensitivity signs and symptoms included generalized macular rash, localized skin reaction, and isolated urticaria or angioedema. All patients received a 20-day course of prednisone, during which 95 percent had resolution of symptoms by a mean of 5 days. All patients were able to complete the minimum desired period of clopidogrel treatment (ie, 1 to 12 months). (See "Antithrombotic therapy for intracoronary stent implantation: General use", section on 'Hypersensitivity'.)
FOOD ALLERGY
Meta-analysis of milk oral immunotherapy studies — A systematic review and meta-analysis of trials evaluating the effectiveness of milk oral immunotherapy found that the likelihood of developing full tolerance to cow’s milk was 10-fold higher and partial tolerance 5-fold higher in children treated with milk oral immunotherapy (OIT) compared with a milk elimination diet in four randomized trials [8]. Results were similar in observational studies. However, there were concerns about the quality of the evidence, including possible publication bias. Additionally, the risk of an adverse reaction to therapy was 34-fold higher in children receiving OIT compared with an elimination diet. (See "Future therapies for food allergy".)
IMMUNODEFICIENCY
Newborn screening for B cell defects — Immunoglobulin kappa-deleting recombination excision circles (KRECs), formed during allelic exclusion, are not produced in patients with B cell maturation defects, such as X-linked agammaglobulinemia. KRECs can be used to screen for early B cell maturation defects from dried blood spots on newborn screening cards using PCR, similar to using T cell receptor excision circles (TRECs) to screen for T cell defects [9]. Simultaneous screening for both T and B cell deficiencies from the same newborn screening card sample is possible using TRECs and KRECs and is undergoing further study [10]. Newborn screening is of potential value in these disorders, since early diagnosis and therapy will prevent some infections. (See "Agammaglobulinemia", section on 'Newborn screening' and "Severe combined immunodeficiency (SCID): An overview", section on 'Newborn screening'.)
Prognosis of patients with common variable immunodeficiency — Data from long-term follow-up of 473 patients with common variable immunodeficiency (CVID) demonstrated that substantial numbers still succumb to the disease, despite significant advances in recognition and treatment [11]. Over a 40 year period, approximately 20 percent died, at the median ages of 44 and 42 for females and males, respectively. The leading causes of death were respiratory failure due to chronic lung disease, lymphoid and other malignancies, and overwhelming infections. (See "Treatment and prognosis of common variable immunodeficiency", section on 'Prognosis'.)
WIP deficiency similar to Wiskott-Aldrich syndrome — A female infant presenting with typical Wiskott-Aldrich syndrome (WAS) symptoms and laboratory findings was found to have a homozygous nonsense mutation in WIPF1 that encodes WASp-interacting protein (WIP) [12]. Both WIP and WASp were absent in the patient’s leukocytes. This case illustrates that WAS cannot be diagnosed solely on the basis of lack of WASp expression, but may require sequence analysis of the WAS gene. WIP deficiency should be suspected in patients with features of WAS in whom WASp is absent, but WAS sequence and mRNA levels are normal. (See "Wiskott-Aldrich syndrome", section on 'WIP deficiency'.)
Primary immunodeficiency and atopy — Children with atopic disease are more likely to develop recurrent and persistent upper respiratory infections, such as sinusitis, rhinitis, and otitis media. However, recurrent infections in atopic children may also be due to a coexisting primary immunodeficiency. In a small retrospective series of children evaluated for primary immunodeficiency, 31 percent who had evidence of antigen-specific IgE by skin prick or blood testing were diagnosed with an immunodeficiency compared with 9 percent of those who were negative on specific IgE testing [13]. Atopic disease and immunodeficiency are both manifestations of immune dysregulation. (See "Approach to the child with recurrent infections", section on 'The child with atopic disease'.)
Rituximab and vaccine response — The impact of rituximab (anti-CD20) on vaccine response has been a concern in patients receiving the drug who may require various immunizations. The effect of rituximab, compared with placebo, on existing antibody levels and on antibody responses to vaccines given concurrently and 12 months after therapy (ie, a time sufficient for B cell recovery) was evaluated in a randomized trial of 75 patients with type I diabetes mellitus [14]. Pre-existing titers to routine vaccines were not affected. During the time of B cell depletion, rituximab recipients had a significantly decreased antibody response to vaccination, although responses normalized with B cell recovery. (See "Secondary immune deficiency induced by drugs and biologics", section on 'Rituximab'.)
RHINITIS AND RHINOSINUSITIS
A rare complication of nasal irrigation — Two fatal cases of primary amebic meningoencephalitis were reported in patients in the state of Louisiana, resulting from the use of unclean tap water to irrigate the sinuses [15]. The causative amoeba was Naegleria fowleri, an organism that is usually contracted from swimming in freshwater lakes and rivers, geothermal bodies of water, or inadequately chlorinated pools [16]. Although this infection is rare, patients who perform sinus irrigation should be advised to use distilled, sterilized, or previously boiled water if making their own saline solutions. (See "Pharmacotherapy of allergic rhinitis", section on 'Nasal saline irrigation'.)
URTICARIA AND ANGIOEDEMA
Gynecologic and obstetric care of women with hereditary angioedema — An international expert panel produced guidelines on the gynecologic and obstetric care of women with hereditary angioedema [17]. The guideline reviews the impact of menstruation, pregnancy, lactation, and menopause on disease activity. Options for contraception are summarized and information regarding treatment of infertility and hormonal treatments for breast and cervical cancers are reviewed. (See "Prevention of attacks in hereditary angioedema", section on 'Gynecologic and obstetric care'.)
VACCINES
Pneumococcal conjugate vaccine in adults — In December 2011, the 13-valent conjugate pneumococcal vaccine (PCV13) that is used routinely in children was approved by the US Food and Drug Administration (FDA) for use in adults ≥50 years of age based upon safety and immunogenicity data [18]. These data showed that PCV13 induced antibody responses that were either comparable to or higher than the responses induced by the pneumococcal polysaccharide vaccine (PPSV23) [18,19]. It appears to have a similar safety profile as PPSV23. PCV13 has not yet been recommended by the United States Advisory Committee on Immunization Practices. (See "Pneumococcal vaccination in adults", section on 'Conjugate vaccines'.)
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.
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