Abstract: Pollinosis is defined as the appearance of respiratory symptoms (rhinoconjunctivitis and/or asthma) as a result of the inhalation of pollen to which the individual is sensitized. Pollen allergy becomes all the more relevant on taking into account that it may be responsible for the development of plant food allergy, or may even constitute the direct cause of esophageal, gastric and/or intestinal inflammation in the context of a digestive allergic process. Pollen can act as a source of allergens that induce primary sensitization in the host as a result of inhalation, with secondary allergy to plant foods containing shared allergens via a cross-reactivity mechanism. The observed pattern of plant food allergy depends on the dietary habits of the population in a given geographical setting, and on the pollination found in that setting. Pollinosis may account for the greater or lesser prevalence of allergy to certain plant foods, and for the severity of the associated reactions. Beyond the digestive tract inflammation that may result from allergy to a given food, pollinosis is also intrinsically able to generate a clinically relevant or irrelevant Th2-mediated inflammatory response at digestive level, and may even give rise to eosinophilic esophagitis. Inter-relation with the airway may also extend to the digestive tract as a consequence of the systemic response that characterizes allergic disease.
Abstract: OBJECTIVE: Allergic rhinitis can determine the presence and type of asthma. The main aim of this study was to evaluate the link between allergic rhinitis, asthma, and skin test sensitization in patients with allergic rhinitis. METHODS: Patients with allergic rhinitis, aged 10 to 50 years, were consecutively enrolled at different allergy centers in Spain and Portugal. All the patients underwent skin prick tests with a panel of 20 biologically standardized aeroallergens. Allergic rhinitis was classified according to etiology and the Allergic Rhinitis and its Impact on Asthma guidelines and asthma was classified according to the Global Initiative for Asthma guidelines. RESULTS: A total of 3225 patients, with a mean age of 27 years, were evaluated. House dust mites and grass and olive tree pollens were the most common aeroallergens. The mean (SD) number of positive skin tests per patient was 6.5 (4), the mean wheal size was 42.3 (28) mm2, and the mean atopy index was 6.5 (2). Forty-nine percent of the patients had concomitant asthma. Asthma severity was associated with a longer time since onset (P < .04) and allergic rhinitis severity (P < .001). Patients with concomitant asthma had a significantly higher number of aeroallergens and sensitization intensity than those without asthma (P < .001). CONCLUSIONS: In this broad population sample, the presence and type of asthma was influenced by skin sensitization and both time since onset and severity of allergic rhinitis.
Abstract: BACKGROUND: Guidelines including level of evidence and grade of recommendation were recently published for chronic urticaria (CU). OBJECTIVES: To describe the therapeutic approach in patients with CU, and to depict how recent guidelines are implemented in the daily practice of management of CU. METHODS: We performed a cross-sectional multicentre study through a questionnaire answered by 139 specialists. In total, 695 patients were evaluated, mean+/-SD age 42.3+/-15 years, 62.1% women. Of the patients, 168 were treated by an allergist, 473 by a dermatologist and in 54 cases the specialist was not stated. The drug prescribed was the main variable, and chi2 and Fisher's tests were utilized for the statistical analysis. RESULTS: Nonsedating anti-H1 antihistamines taken regularly were the most common drugs prescribed, followed by nonsedating anti-H1 antihistamines taken as needed, corticosteroids, sedating antihistamines taken regularly, sedating antihistamines taken as needed, anti-H2 antihistamines, leukotriene antagonists, ciclosporin and doxepin. Nonsedating antihistamines plus corticosteroids was the most frequent drug combination prescribed. When comparing between allergists and dermatologists we found a positive and significant correlation only between prescription of cetirizine, dexchlorfeniramine, leukotriene antagonists and anti-H2 antihistamines and being treated by an allergist. A positive correlation was found with desloratadine and being seen by a dermatologist. We did not find any difference in CU management in the rest of the treatments studied. CONCLUSIONS: It is surprising that a large amount of sedating antihistamines was prescribed. In many instances these were prescribed as needed. This fact could have a negative impact on urticaria control and patient satisfaction. It seems difficult for the nonexpert to differentiate between CU and any kind of physical urticaria.
Abstract: Recently, functional genetic variants of the PTGDR gene have been associated with asthma. The objective of this work was to study polymorphisms of the promoter region of PTGDR and their haplotype and diplotype combinations in a Spanish population of children with asthma. In this study, 200 Caucasian individuals were included. Asthma was specialist-physician diagnosed according to the ATS criteria. The polymorphisms were analyzed by direct sequencing. In the study, the new polymorphism (-613C > T) in the promoter region of PTGDR was analyzed. The CT genotype was more common in controls (17%) than in patients with asthma (1%) (p-value = 0.0003; OR, 0.057; 95% CI, 0.007-0.441). The CCCT CCCC diplotype (promoter positions -613, -549, -441, and -197) was more frequent in the group of patients with asthma [Fisher's p-value = 0.012; OR, 10.24; 95% CI (1.25-83.68)]; this diplotype is unambiguous. To our knowledge, this is the first study of -613C > T PTGDR polymorphism in patients. This analysis provides more complete information on influence of diplotype combinations of PTGDR polymorphisms in asthma.
Abstract: Allergic conjunctivitis is the most common form of ophthalmological allergy. Eye symptoms are one of the main and most frequent reasons for consultation among patients with allergic rhinoconjunctivitis, which in turn is the most common reason for visiting the allergologist, according to the Alergológica 2005 study. Itching is the key symptom of allergic conjunctivitis, and its relief is the principal objective of the broad range of treatment options available. Topical antihistamines with multiple actions (mast cell stabilization, and antiinflammatory and antihistaminic actions) are probably the best treatment option, thanks to their rapid action, safety and convenience of use. However, oral antihistamines (preferentially second generation drugs) can also play an important role, since they are of established efficacy and offer adequate treatment of the nasal symptoms that tend to accompany the ocular manifestations of allergic rhinoconjunctivitis. Models of allergic conjunctivitis are useful for investigational purposes and for advancing our knowledge of allergic reactions. Advances in the study of the physiopathology of ocular allergy allow us to introduce new therapeutic options for the management of such allergic reactions, thanks to the findings derived from models of this kind. The present review provides an update to the published data on allergic conjunctivitis and the current role of both topical and ocular antihistamines in treating the disorder.
Abstract: Recombinant and purified allergens are currently available for determining specific IgE targeted to different allergenic components. In this way it is possible to diagnose the sensitization profile of each individual patient. The microarray technique makes it possible to determine specific IgE against multiple allergens simultaneously in one same patient, with a minimum amount of serum, and even allows the determination of IgG and IgM against the same allergens in one same serum sample. Microarray procedures are being developed not only for the determination of antibodies but also for cell activation tests. In addition, microarray technology will help explain cross-reactions, and will facilitate the evaluation of subjects in which skin tests cannot be performed. These techniques will allow a great step forward in the development of immunotherapy specifically targeted to the sensitizations found in each individual patient, yielding especially hypoallergenic forms of great immunogenic capacity, and thus improving the safety and efficacy of immunotherapy. Lastly, microarrays will improve our understanding of the physiopathology of allergic diseases.
Abstract: BACKGROUND: Allergic rhinitis (AR) is considered to be the most frequent allergic disorder. OBJECTIVE: To present the data from the Alergológica-2005 on the characteristics of patients with AR. METHODS: An observational, descriptive, cross-sectional epidemiologic study was performed on 4991 patients consulting for the first time in Allergology services in Spain. RESULTS: Fifty-five percent of patients consulting Allergology services for the first time were diagnosed with AR, of whom 65% also had conjunctivitis and 37% asthma. Two out of every three subjects with AR consulted their primary care physician twice in the previous 4 months. One third was treated by another specialist in the preceding year and one of every five required treatment in emergency departments. AR affected the quality of life (SF-12), in some cases causing time off work and school. The most frequently involved allergens were pollens (51%), followed by dust mites (42%). Polysensitization was found in 31% of cases. Antihistamines and nasal topical corticoids were the most widely used drugs. In 38% of patients, treatment with specific immunotherapy was begun. CONCLUSIONS: AR was the leading cause of consultations in Alergológica-2005. Rhinitis was frequently associated with other allergic disorders in 65% of patients with conjunctivitis and 37% with asthma. The illness led to a substantial use of healthcare resources and significantly affected the quality of life of the sufferers.
Abstract: In recent years it has been seen that the nervous and immune systems regulate each other reciprocally, thus giving rise to a new field of study known as psychoneuroimmunology. Stress is defined as a general body response to initially threatening external or internal demands, involving the mobilization of physiological and psychological resources to deal with them. In other words, stress is characterized by an imbalance between body demands and the capacity of the body to cope with them. The persistence of such a situation gives rise to chronic stress, which is the subject of the present study, considering its repercussions upon different organs and systems, with special emphasis on the immune system and--within the latter--upon the implications in relation to allergic disease. Activation of the neuroendocrine and sympathetic systems through catecholamine and cortisol secretion exerts an influence upon the immune system, modifying the balance between Th1/Th2 response in favor of Th2 action. It is not possible to affirm that chronic stress is intrinsically able to cause allergy, though the evidence of different studies suggests than in genetically susceptible individuals, such stress may favor the appearance of allergic disease on one hand, and complicate the control of existing allergy on the other.
Abstract: The development of allergic rhinitis entails a complex interaction between genetic predisposition and environmental exposure to different factors, of which the most important is the implicated allergen. There is a clear hereditary component in allergic rhinitis that has been well corroborated by segregation studies and investigations in twins. From the strictly genetic perspective, it is believed that the disease may be the result of the interaction of different genetic alterations, each of which would contribute a small defect. In recent years, considerable attention has focused on the genes that may be implicated in allergic rhinitis. A number of genomic searches have been made, yielding different chromosomal associations--the most repeated being those involving chromosomes 2, 3, 4 and 9. Single-nucleotide polymorphism studies involving genes encoding for molecules implicated in the pathogenesis of allergic rhinitis have also been made. Such molecules comprise chemokines and their receptors, interleukins and their receptors, eosinophil peroxidase and leukotrienes, among others.
Abstract: Allergic rhinitis is presently the most common chronic disorder in the pediatric population. It can affect sleep at night and cause daytime sleepiness, with school absenteeism, "presenteeism" or inattention, mood disturbances and psychosocial problems. All this in turn can contribute to reduce school performance. The correct treatment of allergic rhinitis can improve school performance, though the first generation antihistamines have unacceptable central and anticholinergic effects that can actually worsen the situation. The second generation antihistamines constitute the drug treatment of choice for allergic rhinitis in children. Vasoconstrictors should not be used in pediatric patients, due to their unpredictable pharmacokinetics and very narrow therapeutic margin. Intranasal corticoids could improve school performance in some patients, by reducing nose block or congestion, the nocturnal sleep disturbances, and daytime sleepiness. Concrete studies of the impact of chromones, anticholinergic agents, antileukotrienes and immunotherapy upon school performance are lacking.
Abstract: Understanding how class switch recombination (CSR) is regulated to produce immunoglobulin E (IgE) has become fundamental because of the dramatic increase in the prevalence of IgE-mediated hypersensitivity reactions. CSR requires the induction of the enzyme AICDA in B cells. Mutations in AICDA have been linked to Hyper-IgM syndrome (HIGM2), which shows absence of switching to IgE as well as to IgG and IgA. Although isolated IgE deficiency is a rare entity, here we show some individuals with normal serum IgM, IgG, and IgA levels that had undetectable total serum IgE levels. We have analyzed the AICDA gene in these individuals to determine if there are mutations in AICDA that could lead to selective IgE deficiency. Conformational sensitive gel electrophoresis (CSGE) and sequencing analysis of AICDA coding sequences demonstrated sequence heterogeneity due to 5923A/G and 7888C/T polymorphisms, but did not reveal any novel mutation that might explain the selective IgE deficit.
Abstract: At present, cephalosporins represent one of the most prescribed classes of antibiotics. Although allergic reactions have been estimated to be infrequent, the number of reactions to cephalosporins is increasing due to their wide use. Cross-reactivity with penicillins has mainly been evaluated in patients with penicillin allergy. It is higher between first- and second-generation cephalosporins with the same or similar side chain than between cephalosporins with different side chains. Unlike penicillins, cephalosporin haptens or determinants have not been defined, and therefore the diagnosis is complicated. Nevertheless, skin tests with cephalosporins are useful in the evaluation of several allergic reactions. Although more studies are necessary, a negative result in skin testing to penicillin and cephalosporins with different side chains seems to be a good predictor of tolerance, and could be used in select cases.
Abstract: 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.
Abstract: OBJECTIVES: The aim of this study was to develop a Spanish version of the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) and to test its acceptability, reliability, validity, and sensitivity to change. METHODS: Forward and back translation by bilingual translators followed by pilot testing in patients with urticaria was used to adapt the questionnaire. The Spanish version of the CU-Q2oL was self-administered alongside the Skindex-29 in an observational, longitudinal, multicenter study. Feasibility was assessed by analyzing missing responses and ceiling and floor effects. Reliability was tested by examining internal consistency (Cronbach alpha). Construct validity was analyzed by examining convergent and discriminant validity with the Skindex-29 and by evaluating the ability of the CU-Q2oL to discriminate between patients according to a clinical classification of severity. Sensitivity to change was analyzed in a subgroup of patients who completed a second visit 4 weeks after baseline. RESULTS: A total of 695 patients were included in the analysis. Mean (SD) age was 42.4 (15.0) years and 62.1% of the sample was female. All of the items on the CU-Q2oL were answered by 91.9% of the sample. Over 15% of patients scored at the floor (best possible health) on 5 of the 6 dimensions. Cronbach alpha coefficients were > 0.80 for all dimensions of the CU-Q2oL, and 0.86 for the overall score. Construct validity was supported by correlations between the CU-Q2oL and the Skindex-29, which generally fulfilled hypotheses, and by the questionnaire's ability to discriminate between groups with different severities of urticaria.The questionnaire was sensitive to change, with an effect size of 1.0 for the overall score in patients reporting an improvement on the health transition scale. CONCLUSIONS: The Spanish version of the CU-Q2oL has shown satisfactory reliability, validity, and sensitivity to change. It is suitable for use as an outcome measure for chronic urticaria patients in clinical and research settings.
Abstract: INTRODUCTION: The cysteinyl leukotrienes (Cys-LTs) are potent inflammatory mediators in asthma. It has been suggested that the different response of patients to Cys-LTs inhibitors could be due to the presence of polymorphisms in the genes implicated in this pathway. METHODS: In this study, polymorphisms 927T > C CYSLTR1 and -444A > C LTC4S were analysed in a Spanish population of 188 individuals (109 asthmatic children and 79 controls). Standardised history, skin prick tests and lung function measurements were performed in all patients. Genotypes were determined by sequencing after PCR amplification. RESULTS: Differences were observed in 927T > C CYSLTR1, regarding the severity of asthma in males. A greater presence of allele C in the population with persistent asthma versus the control group (Fisher's p-value = 0.001; Monte Carlo p-value = 0.003; OR: 12.35; 95 %CI: 2.18-70.00) was observed. Differences were also detected in the combined study of both polymorphisms, among controls and asthmatic patients (Monte Carlo p-value = 0.0002). In the group of males with asthma, an increase of AC variant (-444A LTC4S and 927C CYSLTR1) and a reduction in the AT genetic combination were detected. CONCLUSIONS: The combined study of polymorphisms in genes of the leukotriene pathway could explain the differences observed in the studies reported on polymorphism -444A < C LTC4S individually analysed.
Abstract: OBJECTIVES: To develop and validate an instrument to measure health-related quality of life (HRQOL) specific to patients with allergic rhinitis (AR) and primarily for use in Spanish and Spanish-speaking populations. METHODS: An initial item pool was generated from literature review, focus groups with AR patients, and consultations with clinical experts. Item reduction was performed using clinimetric and psychometric approaches after administration of the item pool to 400 AR patients. The resulting instrument's internal consistency, test-retest (2-4 weeks) reliability, known groups and convergent validity, and sensitivity to change were tested in a longitudinal, observational, multicenter study in 210 AR patients who also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: The new questionnaire took a mean (SD) of 7.1 (5.4) minutes to answer. Floor and ceiling effects were less than 15% on all dimensions. Cronbach's alpha values and intraclass correlation coefficient values for six of the sevendimensions and the overall score exceeded 0.70. Statistically significant differences (P < 0.01) were observed on all ESPRINT-28 dimensions and the overall score between patients with mild (mean overall score 1.97, SD 0.99), moderate (mean overall score 2.78, SD 0.88), and severe AR (mean overall score 3.89, SD 0.87). Patients with persistent AR had worse scores (P < 0.05) on all dimensions than patients with intermittent AR. Correlations between the ESPRINT-28 and the RQLQ were generally as expected. Effect sizes for score changes between the two study visits ranged from 0.96 to 1.76 for individual dimensions and the overall score. CONCLUSIONS: This new, Spanish-developed instrument to measure HRQOL in AR patients has shown good reliability, validity, and sensitivity to change. It has also proved easy to use and administer.
Abstract: BACKGROUND: Allergic diseases are (IgE)-mediated hypersensitivity reactions affecting more than 25% of the world's population. Proteomic technologies have been increasingly used in the field of allergy and include the use of protein microarrays and two-dimensional gel electrophoresis coupled with immunoblotting. METHODS: The literature relevant to proteomic approaches to allergic diseases was searched using MEDLINE database. We reviewed proteomics approaches and applications, focusing specifically on two-dimensional immunoblotting techniques and allergen microarrays. RESULTS: The results obtained show that proteomic approaches using two-dimensional immunoblotting appear to be a powerful strategy for the identification of allergenic proteins. Likewise, the use of allergen microarrays allows a large number of IgE antibodies to be simultaneously identified. CONCLUSIONS: Proteomic approaches are only beginning to be applied to the study of allergy. In the field of in vitro diagnosis, allergen microarrays provide a promising tool not routinely used in the allergy laboratory. In the near future this powerful technique will be used as a standard technique for in vitro diagnosis of allergy.
Abstract: BACKGROUND: Allergic Rhinitis and its Impact on Asthma (ARIA) differentiates mild from moderate/severe patients on the basis of 4 severity items. The high prevalence of moderate/severe patients suggests the need to differentiate between them. OBJECTIVES: To identify the categorization that maximizes discrimination between moderate and severe allergic rhinitis (AR) by using ARIA guidelines. METHODS: Observational, cross-sectional study. Clinical characteristics, nasal symptoms (Total Symptom Score 4), and health-related quality of life (HRQL; Rhinoconjunctivitis Quality of Life Questionnaire and Short Form 12) were assessed. The association of severity items (sleep, daily activities/sport, work/school, and troublesome symptoms) with symptoms and HRQL was analyzed using linear regression models. ANOVA and effect sizes were used to assess differences in symptoms and HRQL among groups defined by the number of affected ARIA items. RESULTS: Nontreated patients (N = 141) with moderate/severe AR were studied. All severity items showed a similar independent association with symptoms and HRQL scores, and there were no interaction effects, indicating that categorization of patients into moderate and severe could be based only on the number of items affected. Effect sizes were highest between patients with 4 affected ARIA items and those with 3, 2, or 1 affected item (effect sizes greater than 0.8 in all comparisons using Rhinoconjunctivitis Quality of Life Questionnaire and Short Form 12 Physical Composite Summary, and greater than 0.5 using the Total Symptom Score 4; P < .001). CONCLUSION: Using ARIA severity items, the criterion that best discriminates AR severity is considering moderate those with 1 to 3 affected items and severe those with 4. CLINICAL IMPLICATIONS: Discrimination between patients with moderate and severe AR should help to obtain homogeneous populations for both research and clinical purposes.
Abstract: Antisense oligonucleotides represent a novel therapeutic approach for manipulation of gene expression in the treatment of respiratory diseases. This methodology is based on the use of synthetic oligonucleotides to inhibit the expression of a specific target gene by inhibiting the function of the corresponding messenger RNA. Inhaled antisense oligonucleotides are therapeutic alternatives in the treatment of respiratory diseases including allergic asthma; however development of this technology is at an early stage and critical questions related to design, biological activity, and target delivery still remain. The present review will discuss the current status of antisense technology and its application in asthma and allergy. It will be focused in some representative patents including considerations on the future clinical prospects.
Abstract: 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.
Abstract: 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.
Abstract: Chronic urticaria is highly prevalent in the general population, and while there are multiple treatments for the disorder, the results obtained are not completely satisfactory. The second-generation H1 antihistamines remain the symptomatic treatment option of choice. Depending on the different pharmacokinetics and H1 receptor affinity of each drug substance, different concentrations in skin can be expected, together with different efficacy in relation to the histamine-induced wheal inhibition test--though this does not necessarily have repercussions upon clinical response. The antiinflammatory properties of the H1 antihistamines could be of relevance in chronic urticaria, though it is not clear to what degree they influence the final therapeutic result. Before moving on to another therapeutic level, the advisability of antihistamine dose escalation should be considered, involving increments even above those approved in the Summary of Product Characteristics. Physical urticaria, when manifesting isolatedly, tends to respond well to H1 antihistamines, with the exception of genuine solar urticaria and delayed pressure urticaria. In some cases of chronic urticaria, the combination of H2 antihistamines may prove effective--though only with common liver metabolism (CYP3A4 isoenzyme-mediated) H1 antihistamines, due to the existence of mutual metabolic interferences. The role of leukotriene antagonists associated to antihistamines in application to chronic urticaria remains to be clearly defined.
Abstract: 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.
Abstract: It is well known that the prevalence of allergic diseases has increased in recent decades in the industrialized world. Exposure to environmental pollutants may partially account for this increased prevalence. In effect, air pollution is a growing public health problem. In Europe, the main source of air pollution due to particles in suspension is represented by motor vehicles--particularly those that use diesel fuel. Diesel exhaust particles (DEPs) are composed of a carbon core upon which high-molecular weight organic chemical components and heavy metals deposit. Over 80% of all DEPs are in the ultrafine particle range (< 0.1 pm in diameter). Air pollutants not only have a direct or indirect effect upon the individual, but also exert important actions upon aeroallergens. Pollen in heavily polluted zones can express a larger amount of proteins described as being allergenic. Through physical contact with the pollen particles, DEPs can disrupt the former, leading to the release of paucimicronic particles and transporting them by air--thus facilitating their penetration of the human airways. Climate change in part gives rise to variations in the temperature pattern characterizing the different seasons of the year. Thus, plants may vary their pollination calendar, advancing and prolonging their pollination period. In addition, in the presence of high CO2 concentrations and temperatures, plants increase their pollen output. Climate change may also lead to the extinction of species, and to the consolidation of non-native species--with the subsequent risk of allergic sensitization among the exposed human population. In conclusion, there is sufficient scientific evidence on the effect of air pollution upon allergens, increasing exposure to the latter, their concentration and/or biological allergenic activity.
Abstract: Drugs with antihistamine action are among the most commonly prescribed medicines in pediatrics. According to the International Medical Statistics (IMS), almost two million antihistamine units (in solution) for pediatric use were sold in Spain during 2006--at a cost of nearly 6 million euros. Of this amount, 34% corresponded to first-generation (or sedating) antihistamines. The difficulties inherent to research for drug development increase considerably when the pediatric age range is involved. The use of any medication in this age group must adhere to the strictest safety criteria, and must offer the maximum guarantees of efficacy. For this reason, detailed knowledge of the best scientific evidence available in relation to these aspects is essential for warranting drug use. The first-generation antihistamines have never been adequately studied for pediatric age groups, though they are still widely used in application to such patients. In contrast, studies in children have been made with the second-generation antihistamines, allowing us to know their safety profile, and such medicines are available at pediatric dosages that have been well documented from the pharmacological perspective. The present review affords an update to our most recent knowledge on antihistamine use in children, based on the best scientific evidence available.
Abstract: Epidemiological studies have revealed an association between pollution and allergic respiratory diseases. The main pollutants in this sense are nitric oxide, ozone, and particulate matter. The present review on one hand addresses the chemical characteristics of each of these three groups of pollutants and their main sources, and on the other examines their effects upon allergic respiratory diseases--placing special emphasis on the effects of diesel exhaust particles. For each of the pollutants, the underlying mechanisms capable of influencing allergic respiratory diseases are commented. Lastly, an evaluation is made of some of the genetic aspects related to the response to pollutants.
Abstract: Allergic rhinitis is an inflammatory disease of the nasal mucosa, caused by an IgE-mediated reaction after exposure to the allergen to which the patient is sensitized. Histamine is the most important preformed mediator released in the early stage of the allergic reaction, and also contributes to the late phase of the latter, exhibiting proinflammatory effects. Minimal persistent inflammation is a physiopathological phenomenon induced by the presence of an inflammatory cell infiltrate, together with ICAM-1 expression in the epithelial cells of the mucosa exposed to the allergen to which they are sensitized, in the absence of clinical symptoms. This molecule is considered to be an allergic inflammatory marker. The priming effect first described by Connell in 1968 consists of the reduction in the allergen concentration required to elicit a nasal hyper-response when performing a daily nasal exposure test. This implies that with natural exposure to inhaled allergens, small amounts of environmental allergen will maintain the patient symptoms, and thus of course minimal persistent inflammation. Considering the above, it is questionable whether antihistamines should be administered on a continuous basis or upon demand. The antihistamines, and fundamentally the second-generation drugs, have been shown to exert an antiinflammatory effect, and this effect is greater when the drug is administered continuously than when administered upon demand. Likewise, a reduction in treatment cost and an improvement in quality of life among patients treated on a continuous basis has been documented. However, no studies have been specifically designed to clarify the indication of treatment on a continuous basis or upon demand, as occurs in the GINA. As a result, the individualization of treatment according to the concrete characteristics of each patient seems to be the best approach, at least for the time being.
Abstract: 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.
Abstract: 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.
Abstract: BACKGROUND: Allergic rhinitis (AR) is a prevalent allergic disease in Iberian countries, but there are no recent epidemiological studies that characterize this pathology according to clinical classification and aeroallergens sensitisation. This is a clinical study, representative of each country METHODS: Descriptive, observational cross-sectional, population-based study carried-out in Portugal and Spain. 3397 consecutive patients (5 regions in Spain and 3 regions in Portugal) were selected for clinical observation and skin prick tests were carried out using the same panel of standardized aeroallergens. RESULTS: 3225 patients (aged 10-50 years old) completed the study (IC 95%, SE 15). Intermittent rhinitis makes up 36% of the entire sample. Of them, intermittent AR mild forms represented 82% in Spain and 92% in Portugal that is, 87% for Iberian countries. Persistent types of rhinitis showed exactly the same rate of severity in Portugal and Spain, 44% mild and 56% moderate/severe. Seasonal forms represent 37% while 63% were perennial. BA was present in 49% of AR patients. There were significant differences between aeroallergens according to the different regions considered. Mites and grass pollens are the most relevant aeroallergens in Spanish and Portuguese AR patients, while Alternaria showed higher positive rates among 10-20 year old patients. CONCLUSIONS: This study characterizes the AR patients in Iberian countries according to the ARIA classification. No correlation was observed between this classification and the conventional (seasonal/perennial). Our results also characterize the allergic cutaneous pattern of aeroallergen sensitisation using the same panel of standardized allergens and show differences between the different regions analysed.
Abstract: BACKGROUND AND OBJECTIVE: Atopy is a common immunological disorder underlying allergic rhinitis, atopic dermatitis and allergic asthma. There is an association between atopy and the polymorphism Q576R in the IL4RA gene. The aim of this study is to analyze the allelic distribution of the Q576R polymorphism in an atopic and non atopic population and the relationship with total IgE levels and the family history of atopy. PATIENTS AND METHOD: Q576R polymorphism of IL4RA gene was analyzed by PCR-restriction fragment length polymorphism (RFLP) using MspI restriction enzyme in 154 patients from the Allergy Department of the University Hospital of Salamanca. RESULTS: We have not found an association between the R576 allele and higher serum IgE levels nor atopy in this population. Nevertheless, there is an association between this allele and IgE levels in patients with positive skin prick test and family history of atopy. CONCLUSIONS: Our results suggest that the R576 allele could characterize a specific group of patients with a familial history of atopy in whom the presence of this allele may be related to higher levels of serum IgE.
Abstract: BACKGROUND: IL4/IL4RA pathway plays an important role in atopy and asthma. Different polymorphisms in IL4 and IL4RA genes have been described. Particularly, -33C>TIL4 and 576Q>RIL4RA SNPs have been independently associated to atopy and asthma. The purpose of this study was to analyse these polymorphisms in a population of patients with a well-characterized asthma phenotype. METHODS: A total of 212 unrelated Caucasian individuals, 133 patients with asthma and 79 healthy subjects without symptoms or history of asthma or atopy and with negative skin prick tests were recruited. Lung function was measured by spirometry and asthma was specialist physician-diagnosed according to the ATS (American Thoracic Society) criteria and classified following the GINA (Global Initiative for Asthma) guidelines. Skin prick tests were performed according to EAACI recommendations. -33C>TIL4 was studied with TaqMan assay and 576Q>RIL4RA by PCR-RFLP technique. Hardy-Weinberg equilibrium was analysed in all groups. Dichotomous variables were analysed using chi2, Fisher exact test, Monte Carlo simulation test and odds ratio test. To model the effects of multiple covariates logistic regression was used. RESULTS: No statistically significant differences between the group of patients with asthma and the controls were found when the allele and genotype distribution of -33C>TIL4 and 576Q>RIL4RA polymorphisms were compared. However, the T allele of the -33C>TIL4 SNP was more frequent in patients with persistent asthma. Multivariate analysis adjusted for age and sex confirmed that carriers of allele T had an increased risk of persistent asthma (OR: 2.77, 95%CI: 1.18-6.49; p = 0.019). Analysis of combination of polymorphisms showed that patients carrying both the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA had an increased risk of asthma. This association was particularly observed in persistent asthma [Fisher's p value = 0.0021, Monte Carlo p value (after 10(4) simulations) = 0.0016, OR:3.39; 95% CI:1.50-7.66]. CONCLUSION: Our results show a trend of association between the genetic combination of the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA with asthma. This genetic variant was more frequently observed in patients with persistent asthma. As long as this study was performed in a small population, further studies in other populations are needed to confirm these results.
Abstract: Although there are very few reports of human anaphylaxis induced by tick bites, two such cases have recently been seen in Salamanca, Spain. To identify the tick species responsible, salivary-gland extracts from six species of hard tick and two of soft tick were prepared and used as allergens/antigens in skin-prick tests and serological analyses. For each case, the results of the skin tests were positive for several species of hard tick but negative for the soft ticks. ELISA and western blots revealed high titres of IgG against hard ticks (but not soft ticks) in the sera from both cases. However, serum from only one of the cases was found to be ELISA- and western-blot-positive for tick-specific IgE. Accordingly, the anaphylaxis seen in one case was IgE-mediated whereas that in the other case appeared to be IgE-independent. In both cases, most of the tick-specific antibodies only recognized carbohydrate epitopes. High levels of cross-reactivity between the salivary-gland extracts from several species of hard tick made it impossible to identify which species was responsible for each anaphylactic reaction, although the immunological results seem to point to Ixodes ricinus.
Abstract: 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.
Abstract: 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.
Abstract: A case of fixed eruption caused by ciprofloxacin is reported. To our knowledge, no other cases have been published. Cross-sensitivity with another fluoroquinolone has been demonstrated.
Abstract: We present a case of occupational protein contact dermatitis caused by herring in a dolphinarium worker. The in vivo and in vitro tests results indicated a type I allergic mechanism. In vivo cross-reactivity among fish belonging to the Clupeiformes order was observed.
Abstract: Anthranilic acid derivatives are a group of nonsteroidal antiinflammatory drugs that include glafenine and fenamates. We report a woman who had immediate adverse reactions to glafenine and meclofenamate sodium. Skin prick and intradermal tests were performed with solutions of glafenine and meclofenamate in phosphate-buffered saline (PBS) and with the drugs bound to human serum albumin (HSA). Prick and intradermal tests with PBS solutions were negative for both drugs as were prick tests with HSA solutions. Intradermal tests with HSA-glafenine, however, were positive at 20 minutes, and at 6 and 24 hours. Intradermal tests with HSA-meclofenamate elicited a positive response at 6 and 24 hours. These tests were negative when performed in control subjects. A leukocyte histamine release test and a RAST assay were negative for both drugs. The patient was challenged following a double-blind placebo-controlled oral procedure and tolerated therapeutic doses of aspirin, indomethacin, ibuprofen, dipyrone, diclofenac, piroxicam, and acetaminophen. The oral challenge with glafenine and meclofenamate reproduced the reactions (eliciting doses: 50 mg and 15 mg, respectively), and the patient also reacted to 30 mg of mefenamic acid, an anthranilic acid derivative she had never previously received. This is an exceptional case of selective adverse reactions to glafenine and fenamates, anthranilic acid derivatives, in a patient tolerating aspirin and other cyclooxygenase inhibitors. Our study implicates an immunologic mechanism, and the existence of cross-reactivity between the drugs (or some active metabolite generated in vivo).
Abstract: Ranitidine is a well-tolerated H2-receptor antagonist with a furan ring as nucleus. Anaphylactic reactions are seldom reported despite the wide use of the drug. We report a patient who presented an anaphylactic reaction with ranitidine (Zantac). The positive skin prick test and oral challenge suggest type I hypersensitivity. Specific IgE determination by RAST technique and histamine release test with ranitidine were negative. The patient did not react to other H2-receptor antagonists or to another furan-derivative (nitrofurantoin).
Abstract: Cross-reactivity between quinolones is uncertain. Recently, we studied three patients who had developed suspected allergic reactions to a quinolone. For all of them we performed skin test, histamine release test, RAST, and oral provocation with the suspected quinolone and also with another quinolone of the opposite generation. Five atopic and five nonatopic subjects were used as controls. Neither skin test, histamine release test, nor RAST was useful in the diagnosis. By means of oral controlled provocation, the reactions were reproduced, and all the patients also reacted to another quinolone. We concluded that cross-reactivity between quinolones seems to be very important, and avoidance of any quinolone should be recommended to any patient who has suffered an allergic reaction to one of these drugs.
Abstract: We present two cases of hypersensitivity to cefazolin (one anaphylaxis). The skin prick tests with cefazolin at therapeutic concentration were positive. For the in vitro study we used conjugates of cefazolin with human serum albumin, obtaining a positive result in the histamine release test in both patients. In one case, we demonstrated anticefazolin-specific IgE antibodies by RAST. The controls did not react to any of these tests. Finally, we carried out skin tests and challenge tests with other betalactam antibiotics, including benzylpenicillin, amoxicillin, aztreonam, cefuroxime and cefotaxime, showing in both patients good tolerance to all these drugs.
Abstract: Since 1979 several reports of contact urticaria due to natural latex have been documented. In recent years cases of anaphylaxis, rhinitis, and asthma due to latex have appeared. Nine patients, studied in our clinic between 1986-1991, suffered immediate allergic reactions caused by rubber products. All showed an immediate skin reaction to latex extract. Rub testing with surgical gloves was positive in eight patients. Immunological techniques (RAST, ELISA, HRT) demonstrated specific IgE against latex. Specific bronchial provocation testing was performed in one patient who presented with asthma when she used latex surgical gloves. Patch testing to common rubber additives were negative in our patients. These results suggest that natural latex antigens present in rubber objects can cause hypersensitivity reactions probably due to IgE-mediated mechanisms.
Abstract: We present two patients who experienced life-threatening immediate reactions and one patient who developed generalized urticaria following oral administration of trimethoprim (TMP) and sulfamethoxazole (SMX) combination. Skin prick tests with TMP were positive in the three patients. No patients reacted to skin prick tests with SMX. No significant levels of IgE antibodies to TMP were found by RAST in the serum of the patients. Normal subjects used as controls did not react to any of these tests. Single-blind, placebo-controlled oral challenges were positive with TMP and negative with SMX in all patients. These results suggest that the three patients developed type I hypersensitivity reactions to TMP. In our patients skin prick tests with TMP were useful in TMP hypersensitivity diagnosis.
Abstract: Allergy to vegetables and fruits seems to be more prevalent in atopics, especially in birch pollen-sensitized individuals. We report a case of a grass pollen-sensitized woman, in whom the inhalation of vapor from boiling Swiss chard precipitated rhinoconjunctivitis and asthma. Type I hypersensitivity to Swiss chard was demonstrated by means of immediate skin test reactivity, specific IgE determination by RAST, basophil degranulation, histamine release test, and an immediate bronchial provocation test response to Swiss chard extract. The controls did not react to any of these tests. RAST inhibition assays suggest the presence of some cross-reactivity among Swiss chard and grass pollen antigens, as well as cross-reactivity between vegetables and weed pollens of the chenopod family.
Abstract: A 54-year-old man was receiving calcium dobesilate for retinopathy and after 8 days he presented fever of more than 39 degrees C, generalized myalgia, chills and headache. Other causes of fever were ruled out. A challenge test was done with a single therapeutic oral dose of calcium dobesilate and fever appeared 20 h later and lasted 8 h. Our patient fulfils Young's stringent criteria for drug fever. To our knowledge drug-induced fever due to calcium dobesilate has not been reported previously.
