A Prospective Study of Costs Associated With the Evaluation of Allergic Reactions to Radiological Contrast Media.

BACKGROUND AND OBJECTIVE: The prevalence of hypersensitivity reactions to radiological contrast media (RCM) is increasing owing to the improved performance of diagnostic and therapeutic tests that require RCMs. Objective: We carried out a year-long real-life observational study to prospectively evaluate patients referred to the allergy department from primary care, the emergency department, and other specialties with suspected moderate-to-severe RCM hypersensitivity reactions. METHODS: To study the costs of evaluating RCM hypersensitivity reactions, we systematically recorded direct and indirect costs. RESULTS: Sixty-nine patients with previous reactions to RCM were evaluated in the allergy department from June 1, 2017, to May 31, 2018.Total direct health care costs were €10 715.84, with a mean (SD) cost per patient of €155.30 (77.08). Specifically, direct non-health care costs reached €1605.42 (mean, €23.27 [41.14]), and indirect costs were €6490.85 (mean, €94.07 [110.61]). In summary, the total cost was €18 812.11, that is, a mean cost of €272.64 (164.77). CONCLUSION: Our study shows that the costs of an elective evaluation of hypersensitivity reactions to RCM are low, thus confirming that correct and safe management of affected patients are cost-effective. Therefore, our efforts should be directed toward ensuring the necessary logistics.

A Comprehensive Prospective Study of the Costs Associated With Evaluation of ß-Lactam Allergy.

BACKGROUND AND OBJECTIVE: Being labeled as allergic to penicillin (unverified ß-lactam allergy) can result in patients receiving broader-spectrum antibiotics than necessary that may be more toxic, less effective, and/or more expensive than alternative options. Objective: We aimed to evaluate the real costs of evaluating ß-lactam allergy. METHODS: We performed a prospective real-life observational study designed to evaluate all adult patients who consulted for suspected ß-lactam allergy over a 1-year period. Direct and indirect costs were systematically recorded. Direct health costs were calculated based on the number of visits and all additional and diagnostic tests performed, direct nonhealth costs based on the number of visits and the distance from their homes to the Allergy Department, and indirect costs based on absenteeism. RESULTS: A total of 296 patients with suspected allergy to ß-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct health care costs were €28 176.70, with a mean (SD) cost of €95.19 (37.20). Direct nonhealth costs reached €6551.73, that is, €22.13 (40.44) per patient. Indirect health costs reached €20 769.20, with a mean of €70.17 (127.40). In summary, the total cost was €55 497.63, that is, a cost per patient of €187.49 (148.14). CONCLUSIONS: When all possible costs are taken into account, the evaluation of ß-lactam allergy is not expensive and can reduce future expense arising from unnecessary use of more expensive and less effective antibiotics.

Performance in real life of the European Network on Drug Allergy algorithm in immediate reactions to beta-lactam antibiotics.

European Network on Drug Allergy (ENDA) has proposed an algorithm for diagnosing immediate beta-lactam (BL) allergy. We evaluated its performance in real life. During 1994-2014, 1779 patients with suspected immediate reactions to BL were evaluated following ENDA's short diagnostic algorithm. Five hundred and nine patients (28.6%) were diagnosed of BL hypersensitivity. Of them, 457 (25.7%) were at first evaluation [403 by skin tests (ST), 12 by positive IgE and 42 by controlled provocation tests (CPT)]. At second evaluation (SE), 52 additional patients (10.2% of allergic patients) were diagnosed, [50 (2.8%) by ST and 2 (0.1%) by CPT]. Time between reaction and study was significantly longer in patients diagnosed at SE (median 5 vs 42 months; IQR 34 vs 170; P < 0.0001). Anaphylaxis was significantly associated with a diagnosis at SE. European Network on Drug Allergy/EAACI protocol was appropriate and safe when evaluating BL immediate reactions. Re-evaluation should be performed, particularly when anaphylaxis and long interval to diagnosis are present.

Adverse reactions to immunotherapy are associated with different patterns of sensitization to grass allergens.

The aim of the study was to investigate whether adverse drug reactions (ADRs) during immunotherapy with a grass extract (AVANZ® Phleum, ALK-Abelló) are related to the different patterns of sensitization of patients to grass allergens. A total of 192 patients with rhinitis and/or asthma sensitized to grass pollen received a 4-week updosing with five injections. ADRs were evaluated following EAACI guidelines. A total of 432 ADRs in 133 (69%) patients were recorded, 64% local and 31% systemic. There was a significant association between the number of grass allergens that sensitized the patients and the total number of ADRs (P = 0.004) occurred locally (P = 0.003) and systemically (P = 0.01). Sensitization to Phl p1 + Phl p5 or Phl p1 + Phl p5 + Phl p12 was significantly associated with a higher frequency of local or systemic reactions (P = 0.001, both). Different patterns of sensitization to grass allergens may potentially be considered a risk marker to the development of ADRs to immunotherapy.

(CCTTT)n polymorphism of NOS2A in nasal polyposis and asthma: a case-control study.

BACKGROUND: Nitric Oxide (NO) has been proposed as an important signaling molecule. NO produced by the inducible NO synthase enzyme NOS2A is generated at high levels in certain types of inflammation. A pentanucleotide polypyrimidine microsatellite CCTTT has been identified in the promoter region of the NOS2A gene. OBJECTIVE: The aim of this study was to analyze the (CCTTT)n polymorphism in patients with asthma and nasal polyposis. MATERIAL AND METHODS: The study included 292 white individuals (194 patients and 98 controls). Asthma was diagnosed according to American Thoracic Society criteria and classified in accordance with the guidelines of the Global Initiative for Asthma. Skin prick tests were performed in all individuals. The polymorphism was analyzed by an electrophoretic method and by direct sequencing. RESULTS: A significant association was detected for a 15-repeat cutoff in nasal polyposis (Fisher P value = .0001, Monte Carlo P value [after 10(4) simulations] = .002). Multivariate analysis adjusted for age and sex confirmed this association with an increased risk of nasal polyposis (odds ratio, 14.39; 95% confidence interval, 3.02-68.60; P = .001). CONCLUSION: The number of CCTTT repeats in the promoter region of NOS2A could be associated with the inflammatory process of nasal polyposis in our population. Modifications of NOS2A transcription levels could be involved in this association.

Selective immediate hypersensitivity to cefepime.

Cefepime is a fourth-generation cephalosporin with a broad antimicrobial spectrum and good activity against both gram-positive and gram-negative organisms. We present the case of a 61-year-old man who developed an immediate urticarial reaction after receiving a single dose of cefepime. Skin tests were positive to cefepime and negative to the other beta-lactam antibiotics. Controlled administration of amoxicillin-clavulanic acid and ceftazidime was well tolerated by the patient. To the best of our knowledge, this is the first report of selective hypersensitivity to cefepime demonstrated by skin and challenge tests. Complete allergological studies, including challenge tests with other beta-lactam antibiotics that produce a negative result in skin tests, should be considered in these patients.

Analysis of 927T> C CYSLTRI and -444A > C LTC4S polymorphisms in patients with asthma.

BACKGROUND: The cysteinyl leukotrienes (cys-LTs) are proinflammatory mediators synthesized through the 5-lipoxygenase pathway of arachidonic acid metabolism. Cys-LTs exert their biological action by binding two types of G-protein-coupled seven transmembrane receptors, CYSLTR1 and CYSLTR2. The contribution of the cys-LT receptors to bronchial asthma has been established by the therapeutic efficacy of biosynthetic inhibitors and selective CYSLTR1 blockers. OBJECTIVE: The present study was designed to analyse two different polymorphisms 927T>C CYSLTR1 and -444A>C LTC4S, and to determine whether there is an association between these polymorphisms and the asthma phenotype in a Spanish population. METHODS: Both single nucleotide polymorphisms (SNPs) were analysed in 208 individuals (130 asthmatic subjects and 78 controls). A standardized history, physical examination, skin prick tests and lung function measurement were taken from all patients. Genotypes were determined by direct sequencing after polymerase chain reaction (PCR) amplification. RESULTS: In the group of male patients, the C allele of 927T> C CYSLTRI was more common among patients with asthma than controls. No association was detected between the -444A> C LTC4S polymorphism and the asthma phenotype. The combination of 927T CYSLTR1 and -444A LTC4S was less common in male patients with asthma than in controls (Fisher's P-value =.039; Monte Carlo P-value (after 104 simulations)= .045 and the combination of 927C CYSLTR1 and -444A LTC4S was slightly more frequent in patients with asthma. No differences were observed in the female group. CONCLUSIONS: The results suggest a certain trend of associations that could help to explain some controversial results in association studies of these genes from the leukotriene pathway, when considered individually. Further studies are needed to confirm such an association.

Prevention of allergic diseases.

The prevalence of asthma and allergic diseases has increased in recent years, particularly in the industrialized world. Allergic disease begins to manifest in the first years of life. The disorder usually manifests initially in the form of food allergy and atopic dermatitis, followed in later stages by respiratory allergy with rhinitis and/or asthma. This has led to the adoption of preventive measures in those children with a high risk of atopy, based on the following considerations: 1) A family history of allergic diseases (asthma, eczema, and/or allergic rhinitis); 2) A personal history of atopy such as atopic dermatitis, particularly when associated to food allergy; and 3) The existence of allergic sensitization, particularly to pneumoallergens, of early or late onset, but persistent during childhood. Prevention is established at three different levels: primary prevention, avoiding sensitization; secondary prevention, avoiding appearance of the disease; and tertiary prevention, avoiding the symptoms. The present study discusses current knowledge of prevention and its efficacy, with mention of the importance of breastfeeding and the use of pre- and probiotics for securing adequate prevention.

Usefulness of intradermal test and patch test in the diagnosis of nonimmediate reactions to metamizol.

BACKGROUND: Metamizole is a pyrazolone derivative, and its most common reactions are IgE-mediated reaction and idiosyncratic reactions. Non-immediate reactions are poorly described and there are very few reports on non-immediate reactions to pyrazolones. MATERIALS AND METHODS: We evaluated 12 patients (nine men) who consulted for a non-immediate reaction after metamizol administration. We performed cutaneous tests (skin prick tests and immediate and delayed intradermal tests) and epicutaneous tests, and, if necessary, an oral challenge test. RESULTS: All skin prick and intradermal tests, if necessary, were negative in immediate reading. Delayed intradermal tests were positive in six of 10 patients (60%) and epicutaneous tests were positive in four of 11 patients (36%). Three cases (25%), were diagnosed by a positive oral challenge test. DISCUSSION: Delayed-reading intradermal tests and patch tests are useful tools in the diagnosis of nonimmediate reactions to pyrazolones and should be considered the first step when evaluating these type of reactions. Intradermal test appears to be more sensitive than patch test. The positivity of skin tests suggests an immunological reaction, probably mediated by T lymphocytes, but further studies are required.

Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with asthma.

BACKGROUND: PTGDR gene has been identified as an asthma-susceptibility gene. Recently, functional genetic variants have been associated with asthma. The objective of this work was to study -549T>C, -441C>T and -197T>C PTGDR promoter polymorphisms in a Spanish population. METHODS: In this study, 197 Caucasian individuals were included. Asthma was specialist-physician diagnosed according to the American Thoracic Society (ATS) criteria and classified following the Global Initiative for Asthma (GINA) guidelines. Skin prick tests were performed in all patients. The polymorphisms were analyzed by direct sequencing. RESULTS: -197T>C polymorphism was significantly associated with asthma [Fisher's P-value = 0.007, Monte Carlo P-value (10(4) simulations) = 0.004]. Multivariate analysis adjusted for age and sex confirmed this association with an increased risk of asthma (OR, 3.06; 95% CI, 1.28-7.32; P-value = 0.012). CCT CCC diplotype was associated with asthma (P-value < 0.0001; OR, 1.15; 95% CI, 1.07-1.23), specifically with allergic asthma (P-value < 0.0001). CCT CCC diplotype is unambiguous. All individuals carrying this diplotype had asthma. CONCLUSION: We identified a specific promoter variant of PTGDR that could be associated with asthma. This diplotype is a combination of the two highest transcriptional efficiency haplotypes, recently described. Our in vivo results would support for the first time what was demonstrated in vitro about high-transcriptional efficiency PTGDR haplotypes in asthma.

[Viral infection and asthma: immunologic mechanisms]. / Infección vírica y asma: mecanismos inmunológicos.

The role of viral respiratory infections in lactating infants and other children continues to generate controversy. The debate concerns the difference, or the apparent differences, in the natural history of wheezing. Viral infections frequently provoke wheezing episodes in non-asthmatic small children but in the majority of these the wheezing disappears without the child subsequently developing asthma. In some cases, however, the wheezing persists and in others the child has asthma. Both the role of viral infection and the mechanisms by which wheezing can be produced in a previously healthy child or exacerbated in asthmatic children are unknown. Several hypotheses have been put forward to explain the relationship between viral infections and persistent wheezing and asthma: 1. Altered immune response to various allergens, whether producing sensitization to these allergens or inhibiting tolerance response to airborne allergens. The number of such patients is increasing, among them those with bronchiolitis, asthma, positive skin tests and specific IgE antibodies. Although there is no unanimity on the matter, these patients also present elevated IL-4 levels and reduced IFN-gamma levels. 2. Induction of inflammation typical of allergic asthma. This occurs when the virus interacts with T lymphocytes; (the natural response to viral infection is Th0 and Th1 lymphocyte differentiation and release of IFN-gamma, which has antiviral properties. In children infected with respiratory syncytial virus Th2 lymphocyte differentiation is produced, which is characteristic of allergic reactions, to the detriment of Th1); epithelial cells (in these cells active viral infection activates nuclear transcription kappa-beta and nuclear IL-6 factor, producing the release of numerous pro-inflammatory cytokines and chemokines as well as expression of adhesion molecules); eosinophils (inducing variable eosinophilia which, to a certain degree, has predictive value for the persistence of wheezing) and other inflammatory cells such as neutrophils and macrophages. In the same context, during viral respiratory infection, the presence of mediators (leukotrienes, especially LTC4, histamine, prostaglandins and tryptase) are observed in respiratory secretions and a correlation between levels of specific IgE mediators can be observed. 3. Increased allergic inflammation--producing bronchial hyperreactivity, mediator release by the various inflammatory cells and neuropeptides from C-sensitive fibers, and even interfering with nitric oxide bronchodilators. In spite of all of the above, it seems that recurrent wheezing after childhood bronchiolitis is not exclusively the result of viral infection and that other factors also play a role in this disease.

[Preventive measures for allergic diseases]. / Medidas preventivas de las enfermedades alérgicas.

Allergic diseases, particularly asthma and asthma equivalents, are among the most frequent disorders seen in the pediatric clinic. Approximately 25% of children from developed countries have presented wheezing in recent years, and half of these children later experience major asthma attacks. Likewise, 25% of children between 8 and 11 years have at some time used beta agonists and at least 10% of them use preventive asthma medication. Prevention measures for allergic asthma include: 1) avoiding allergic sensitization; 2) avoiding the presentation of disease in sensitized patients; and 3) preventing symptoms after the disease has appeared. Allergic diseases have a multifactorial origin that includes genetic, perinatal, and specific and non-specific environmental factors. From a genetic point of view, asthma is a multifactorial and heterogeneous pathology with a variable degree of penetration and phenocopy. Allergy is more frequent among the offspring of atopic parents. Genetic variations in different chromosomes affect molecules and receptors involved in atopy: IgE elevation, Fce1 receptor and chromosome 11; IL-4 and chromosome 3; gamma interferon and chromosome 12; TcR a/d receptor and chromosome 14; TcR-beta and chromosome 7; and the main histocompatibility complex HLA I and II and chromosome 6. Likewise, it has been confirmed that genetic variants affect structures in the impact organs, such as the beta 2 receptors of IL-4 soluble receptors, which favor bronchial hyperreactivity. Recently, somatometric measures have been related (low weight and large head circumference at birth) with a later increase in IgE and the occurrence of asthma. The environmental factors most closely involved in the occurrence of asthma are: diet (early exposure to sensitizing foods); domestic, outside, and occupational seroallergens; pollution (particularly smoking and urban and industrial pollution); and infections, particularly viral infections. In the present study, the methods used for the early identification of children at risk are evaluated, as well as the role of the primary care pediatrician in the early detection of allergic children and the interventions that they carry out. Finally, an analysis is made of the preventive measures that should be taken in children at risk of allergic disease, particularly: 1) increasing awareness of health, 2) reduction of exposure to smoking. 3) reduction of urban and industrial pollution, 4) delayed introduction of certain foods, reduction in the level of domestic allergens, 6) control of infections, and 7) pharmacological measures designed to prevent the occurrence of asthma in children.

Hypersensitivity to latex, chestnut, and banana.

The incidence of latex-allergic patients is probably higher than suspected. A spectrum of IgE-dependent allergic reactions to latex products including urticaria, rhinitis, asthma, angioedema, and life-threatening anaphylaxis has been increasingly reported in recent years. We describe three patients with rubber hypersensitivity and allergy to fruit (banana and chestnut). Immediate positive responses were obtained in prick tests with latex, banana, and chestnut extracts. Histamine release was positive and specific IgE antibodies to all three extracts were detected by fluorescence radioimmunoassay. In the RAST-inhibition studies, the extract of latex inhibited the binding of chestnut and banana, but chestnut and banana extracts did not inhibit the binding of latex. These results suggest a sensitivity to crossreacting antigens in latex allergy associated with allergy to certain fruits.