Disclosures: Anna M Feldweg, MD Nothing to disclose. Elizabeth TePas, MD, MS Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
ASTHMA AND COPD
Investigational agent shows promise in asthma (June 2015)
GATA3 is a transcription factor that is essential for Th2 lymphocyte differentiation and activation. An investigational synthetic DNA molecule (SB010) has been developed that uniquely binds to GATA3 messenger RNA and cleaves it. The effect of SB010 was assessed in 43 patients with mild allergic asthma who were randomly assigned to inhalation of SB010 or placebo once daily for 28 days . The early and late asthmatic responses to allergen bronchoprovocation were significantly attenuated by SB010. The degree of suppression of the late response was similar to that of inhaled glucocorticoids. This study supports a potential role for disruption of GATA3 (and thus Th2 cytokines) in asthma. (See "Alternative and experimental agents for the treatment of asthma", section on 'GATA3-specific DNAzyme'.)
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 . 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'.)
Eosinophilia during prolonged antibiotic therapy (June 2015)
Eosinophilia is not uncommon in patients receiving prolonged intravenous (IV) antibiotics, but the prevalence and significance has not been extensively studied. In a prospective cohort study of 824 patients receiving prolonged intravenous antibiotic therapy, eosinophilia developed in 25 percent, appearing at a median of 15 days of therapy and peaking at a median absolute count of 726/mL (500 to 8610/mL) . Although most patients with eosinophilia completed their courses without complications, one-third developed a hypersensitivity reaction involving rash or hepatic or renal involvement. Medication-associated eosinophilia does not mandate discontinuation of therapy but warrants close monitoring for evidence of hypersensitivity and consideration of alternative medications that could be substituted without compromising care. (See "Approach to the patient with unexplained eosinophilia", section on 'Medications and over the counter remedies'.)
Low allergic cross-reactivity between penicillins and carbapenems (May 2015)
Carbapenems (eg, imipenem, meropenem) share a common beta-lactam ring with penicillins and hence the potential for allergic cross-reactivity, and some drug information systems list penicillin allergy as a contraindication to the use of carbapenems (figure 1). In the largest study to date, 212 patients with allergy to penicillins, confirmed by skin testing, were then tested with carbapenems . All subjects were negative to carbapenem skin testing and tolerated graded challenges to three different carbapenems. Based on this and other series, the rate of reactivity to carbapenems in patients with confirmed penicillin allergy is estimated at <1 percent. This supports our current recommendations on administration of carbapenems to patients reporting immediate-type penicillin allergy: Perform penicillin skin testing when available. If negative, patients may safely receive penicillins and carbapenems. If penicillin skin testing is positive or not available, carbapenems may be administered via a graded challenge. (See "Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams", section on 'Carbapenems'.)
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) . 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
Transient transfer of food allergies in a blood product (September 2015)
A recent case report highlights the possibility of acquiring food allergies following transfusion of a blood product such as platelets . This may also occur after solid organ or hematopoietic cell transplantation. In the former case, the allergy is transient and is due to food-specific immunoglobulin E (IgE) in the blood product. In the latter case, the potential mechanism depends upon the type of transplant and can range from temporary allergy due to transferred mast cells or allergen-specific IgE, to longer-lasting or permanent allergy due to transfer of food allergen-specific lymphocytes or hematopoietic stem cells from the donor. Finally, an allergic reaction to a food can occur in an allergic recipient after receiving a blood product that contains intact allergen consumed by the donor. (See "History and physical examination in the patient with possible food allergy", section on 'Questions related to contributory factors'.)
Pulmonary manifestations in adults with chronic granulomatous disease (June 2015)
Pulmonary complications remain the most common manifestation of chronic granulomatous disease (CGD) in adulthood. In a series of 67 adults with CGD, two-thirds had at least one infectious or noninfectious pulmonary event, and about half had manifestations involving the gastrointestinal tract or skin . Most patients with invasive pulmonary fungal infections were on itraconazole prophylaxis, although serum azole concentrations were low in the majority of the patients tested. One-third of patients with pulmonary complications, including invasive fungal infections, were asymptomatic. Serial screening for elevated inflammatory markers, such as C-reactive protein (CRP), followed by imaging of the suspected organ(s) involved if levels are elevated, are suggested to monitor for and diagnose infection. (See "Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Sites of infection' and "Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Pulmonary' and "Chronic granulomatous disease: Treatment and prognosis", section on 'Antifungal prophylaxis' and "Pulmonary complications of primary immunodeficiencies", section on 'Chronic granulomatous disease' and "Chronic granulomatous disease: Treatment and prognosis", section on 'Monitoring and diagnosis'.)
Dedicator of cytokinesis 2 deficiency (June 2015)
Dedicator of cytokinesis 2 (DOCK2) deficiency is a newly recognized combined immunodeficiency (CID). Biallelic (homozygous or compound heterozygous) mutations in the DOCK2 gene were identified through whole-exome sequencing in a group of unrelated patients with early-onset invasive bacterial and viral infections, lymphopenia, and defective T, B, and NK cell responses . DOCK2 deficiency results in impaired activation of RAC1 that leads to defects in actin polymerization, lymphocyte proliferation and migration, natural killer cell degranulation, and response to viral infections in fibroblasts and peripheral blood mononuclear cells. Other CIDs that are the result of defects in actin regulation include Wiskott-Aldrich syndrome and DOCK8 deficiency. (See "Combined immunodeficiencies", section on 'Dedicator of cytokinesis 2 deficiency'.)
URTICARIA AND ANGIOEDEMA
Mechanism proposed for hereditary angioedema with normal C1 inhibitor and FXII mutations (August 2015)
Hereditary angioedema with normal C1 inhibitor is a rare disorder; normal complement studies distinguish this from other forms of hereditary angioedema. Defects in the gene for coagulation factor XII (FXII) are seen in some patients with hereditary angioedema with normal C1 inhibitor but a mechanism linking FXII defects and angioedema has been lacking. A new study proposes that one FXII mutation found in these patients affects a glycosylation site, resulting in increased autoactivation of FXII . Increased FXII autoactivation could lead to enhanced activation of the kallikrein-kinin pathway and excessive bradykinin formation. Thus, a potential mechanism has been identified for the pathogenesis of the hereditary angioedema in patients with normal complement studies and a FXII mutation. (See "Hereditary angioedema with normal C1 inhibitor (type III HAE)", section on 'Mutations in the FXII gene'.)
VACCINES AND VACCINE HYPERSENSITIVITY
Revised schedule for pneumococcal vaccination in older adults (September 2015)
The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for many years in the United States for all adults ≥65 years of age. In 2014, the United States Advisory Committee on Immunization Practices (ACIP) began also recommending the 13-valent pneumococcal conjugate vaccine (PCV13) for adults ≥65 years of age . In September 2015, the ACIP changed the recommended interval between administration of PCV13 and PPSV23 for immunocompetent adults ≥65 years of age from 6-12 months to ≥1 year to simplify the administration schedule (algorithm 1) . In patients who have already received PPSV23, at least 1 year should elapse before they are given PCV13. (See "Pneumococcal vaccination in adults", section on 'Schedule for dual vaccination'.)
US ACIP recommendations for serogroup B meningococcal vaccination (June 2015)
In late 2014 and early 2015, the US Food and Drug Administration approved two serogroup B meningococcal vaccines (Trumenba, MenB-FHbp and Bexsero, MenB-4C). In June 2015, the Advisory Committee on Immunization Practices (ACIP) issued recommendations for serogroup B meningococcal vaccine for high-risk individuals aged 10 years or older; these include individuals with persistent complement component deficiencies, individuals with anatomic or functional asplenia, microbiologists routinely exposed to N. meningitidis isolates, and individuals at increased risk because of a serogroup B meningococcal disease outbreak . These indications overlap with those for the quadrivalent meningococcal conjugate vaccine and are summarized in the table (table 1). Among patients with none of the above risk factors, the ACIP advises discussion between doctors and patients regarding vaccination against serogroup B meningococcus; routine vaccination has not been recommended . (See "Meningococcal vaccines", section on 'Use in United States'.)
OTHER GENERAL ALLERGY AND IMMUNOLOGY
Prediction model for eosinophilic esophagitis (September 2015)
The distinction between eosinophilic esophagitis and gastroesophageal reflux disease is often difficult to make. A prediction model that incorporated eight clinical and endoscopic features (younger age; male sex; presence of dysphagia and food allergies; presence of esophageal rings, furrows, and plaques; and lack of a hiatal hernia) predicted eosinophilic esophagitis with an accuracy, sensitivity, and specificity of 84, 97, and 92 percent, respectively . However, additional studies are needed to validate this model. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis", section on 'Distinction from GERD'.)
Stevens-Johnson syndrome outbreak associated with M. pneumoniae (August 2015)
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, severe blistering mucocutaneous reaction, most commonly triggered by medications, characterized by extensive necrosis and detachment of the epidermis and mucosa. Mycoplasma pneumoniae and cytomegalovirus infections are the next most common trigger of SJS/TEN, particularly in children. Between September and November 2013, an outbreak of eight pediatric cases of M. pneumoniae-associated SJS/TEN was reported in Colorado, likely related to high levels of M. pneumoniae infection in the region . All children had severe oropharyngeal mucositis; the conjunctiva was involved in seven children and the genital mucosa in five. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Infection'.)
Influenza vaccine recommendations for 2015-2016 influenza season (August 2015)
In August 2015, the Advisory Committee on Immunization Practices released recommendations for the prevention and control of influenza during the 2015-2016 influenza season in the United States. As in previous seasons, seasonal influenza vaccination is recommended for everyone ≥6 months of age . Changes for the 2015-2016 season include:
●Different influenza A H3N2 and influenza B (Yamagata lineage) antigens than were in the 2014-2015 vaccines
●A simplified dosing algorithm for children six months through eight years (algorithm 2)
●Availability of a quadrivalent intradermal vaccine for adults 18 through 64 years of age (table 2)
Predictors of the need for repeat epinephrine doses in anaphylaxis (August 2015)
Epinephrine is the first-line therapy for anaphylaxis, and retrospective studies suggest that up to one-third of patients may require a second dose. However, predictive factors for requiring more than one dose are not well defined. In a prospective cohort study of over 500 patients (all ages) treated for anaphylaxis in a tertiary care emergency department, 14 percent of those requiring any epinephrine required more than one dose . Patients with a history of previous anaphylaxis, and those presenting with flushing, diaphoresis, or dyspnea, were more likely to require multiple doses of epinephrine to control symptoms. Anaphylaxis is an inherently unpredictable disorder, but this study provides some insight into predictors of a more complicated treatment course and may help clinicians managing such patients. (See "Anaphylaxis: Rapid recognition and treatment", section on 'Dosing and administration'.)
Ease of use of different epinephrine autoinjectors for anaphylaxis (July 2015)
Epinephrine autoinjectors can be life saving for patients with serious allergies, but even with specific training, many people have trouble using the various devices properly. A randomized trial of mothers of food-allergic children, tested in simulated anaphylaxis scenarios, suggested that the Auvi-Q device, a rectangular cassette that has audible instructions to guide the user through the injection process, was easier to use than non-audible pen devices . When prescribing an epinephrine autoinjector, ease of use, cost, the need for multiple injectors, and patient facility with self-injection should all be considered. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Ease of use'.)
Acute worsening of atopic dermatitis due to aeroallergen exposure (July 2015)
Environmental allergens are a trigger of atopic dermatitis (AD) in a small subset of children and adults. Patients who have environmental allergies as a trigger of AD have persistent disease with chronic exposure to an allergen in the environment. A small study of adults with AD demonstrated that exposure to grass pollen in an environmental challenge chamber for two consecutive days resulted in a significant worsening of AD on exposed skin for the five days after challenge compared with exposure to clean air (placebo) . This study shows that an isolated exposure to an aeroallergen can cause an acute flare of AD in sensitized individuals. (See "Role of allergy in atopic dermatitis (eczema)", section on 'Aeroallergens'.)
Unclear association between atopic dermatitis and lymphoma (May 2015)
The association between atopic dermatitis and lymphoma is controversial. A 2015 systematic review and meta-analysis of four cohort studies and 18 case-control studies found a modest increase in the risk of lymphoma in patients with atopic dermatitis compared with the general population . The risk increase was significant in the meta-analysis of the cohort studies but not in the case-control studies. However, the large heterogeneity of case-control studies in study design and diagnostic criteria does not allow any definite conclusion. In particular, due to overlapping clinical features, cases of cutaneous T cell lymphoma may have been initially misdiagnosed and treated as severe atopic dermatitis. (See "Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)", section on 'Risk of lymphoma'.)
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 . 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'.)
- Krug N, Hohlfeld JM, Kirsten AM, et al. Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme. N Engl J Med 2015; 372:1987.
- Over-the-Counter Asthma Products Labeled as Homeopathic: FDA Statement - Consumer Warning About Potential Health Risks. http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm439014.htm.
- Blumenthal KG, Youngster I, Rabideau DJ, et al. Peripheral blood eosinophilia and hypersensitivity reactions among patients receiving outpatient parenteral antibiotics. J Allergy Clin Immunol 2015.
- Gaeta F, Valluzzi RL, Alonzi C, et al. Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins. J Allergy Clin Immunol 2015; 135:972.
- Ureña-Tavera A, Zamora-Verduga M, Madrigal-Burgaleta R, et al. Hypersensitivity reactions to racemic calcium folinate (leucovorin) during FOLFOX and FOLFIRI chemotherapy administrations. J Allergy Clin Immunol 2015; 135:1066.
- Ching JC, Lau W, Hannach B, Upton JE. Peanut and fish allergy due to platelet transfusion in a child. CMAJ 2015; 187:905.
- Salvator H, Mahlaoui N, Catherinot E, et al. Pulmonary manifestations in adult patients with chronic granulomatous disease. Eur Respir J 2015; 45:1613.
- Dobbs K, Domínguez Conde C, Zhang SY, et al. Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections. N Engl J Med 2015; 372:2409.
- Björkqvist J, de Maat S, Lewandrowski U, et al. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III. J Clin Invest 2015; 125:3132.
- 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.
- Kobayashi M, Bennett NM, Gierke R, et al. Intervals Between PCV13 and PPSV23 Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2015; 64:944.
- Folaranmi T, Rubin L, Martin SW, et al. Use of Serogroup B Meningococcal Vaccines in Persons Aged ≥10 Years at Increased Risk for Serogroup B Meningococcal Disease: Recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep 2015; 64:608.
- http://www.cidrap.umn.edu/news-perspective/2015/06/acip-endorses-individual-choice-meningitis-b-vaccine (Accessed on June 25, 2015).
- Dellon ES, Rusin S, Gebhart JH, et al. A Clinical Prediction Tool Identifies Cases of Eosinophilic Esophagitis Without Endoscopic Biopsy: A Prospective Study. Am J Gastroenterol 2015; 110:1347.
- Olson D, Watkins LK, Demirjian A, et al. Outbreak of Mycoplasma pneumoniae-Associated Stevens-Johnson Syndrome. Pediatrics 2015; 136:e386.
- Grohskopf LA, Sokolow LZ, Olsen SJ, et al. Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 Influenza Season. MMWR Morb Mortal Wkly Rep 2015; 64:818.
- Campbell RL, Bashore CJ, Lee S, et al. Predictors of Repeat Epinephrine Administration for Emergency Department Patients with Anaphylaxis. J Allergy Clin Immunol Pract 2015; 3:576.
- Umasunthar T, Procktor A, Hodes M, et al. Patients' ability to treat anaphylaxis using adrenaline autoinjectors: a randomized controlled trial. Allergy 2015; 70:855.
- Werfel T, Heratizadeh A, Niebuhr M, et al. Exacerbation of atopic dermatitis on grass pollen exposure in an environmental challenge chamber. J Allergy Clin Immunol 2015; 136:96.
- Legendre L, Barnetche T, Mazereeuw-Hautier J, et al. Risk of lymphoma in patients with atopic dermatitis and the role of topical treatment: A systematic review and meta-analysis. J Am Acad Dermatol 2015; 72:992.
- Cheng CM, Hsu JW, Huang KL, et al. Risk of developing major depressive disorder and anxiety disorders among adolescents and adults with atopic dermatitis: a nationwide longitudinal study. J Affect Disord 2015; 178:60.