Importance of hypersensitivity in adverse reactions to drugs in the elderly.

BACKGROUND: The use of drugs in the elderly is very extensive because of the frequent occurrence of chronic diseases. Adverse drug reactions (ADRs) commonly occur in geriatric patients receiving multiple therapeutic regimens. In the literature, little attention has been given to ADRs in the elderly, and particularly to allergic reactions. OBJECTIVE: The aim of the present study is to provide data on possible inappropriate prescriptions in the elderly in relation to allergic reactions and to identify a list of drugs which are likely inducers of allergic reactions. METHODS: We retrospectively evaluated ADRs in patients referring to Immunoallergy Unit of Hospital Policlinico in Bari on the basis of Beers criteria. Among adverse reactions, hypersensitivity reactions were extracted and a comparison between different age groups was assessed. RESULTS: Out of 823 patients with ADRs, in 30.6% hypersensitivity drug reactions (HDR) were diagnosed. Data about drug intake, comorbidities and clinical presentation were collected, aiming to identify possible risk factors. An evaluation of drugs most commonly involved was assessed. CONCLUSIONS: HDR are reported to represent 5-10% of all ADRs, while in our study population the prevalence was about 30%. This suggests the need to develop strategies to minimize the incidence of drug allergy in the elderly, as well to reduce the phenomenon of inappropriate prescriptions.

Low incidence of pneumonia in COPD patients treated with inhaled corticosteroids undergoing pulmonary rehabilitation.

BACKGROUND: Based on meta-analyses results, it is currently acknowledged that there is an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD) undergoing inhaled corticosteroids (ICS) treatment. However, this is not found to be true in those with asthma. No data on this risk are available for COPD patients involved in pulmonary rehabilitation program (PR). METHODS: For 1 year, we prospectively studied 2 cohorts of COPD patients-undergoing PR and not undergoing PR. The first group included 438 patients undergoing PR of which 353 were treated with ICS, and 85 were treated with bronchodilators only. The second group was comprised of 76 COPD patients who were treated with ICS, but not PR. The control group consisted of 49 ICS-treated patients with asthma. The diagnosis of pneumonia, when suspected, had to be confirmed with a chest x-ray. RESULTS: Overall, 6 cases of pneumonia were diagnosed in the first study group: 5 ICS-treated patients and 1 patient treated only with bronchodilators. This corresponded to a rate of 1.41 and 1.17%, respectively, compared to a rate of 6.6% in COPD patients not treated with PR, which was significantly higher (p = 0.029) than that in the first study group. No case of pneumonia was registered among patients with asthma. CONCLUSIONS: These findings suggest that a significantly lower incidence of pneumonia is found in COPD patients treated with ICS and PR than in patients treated with ICS but not with PR. This observation deserves to be investigated in large populations of PR-treated COPD patients, possibly in multi-centric cohort studies.

Preventive actions of allergen immunotherapy: the facts and the effects in search of evidence.

Allergen immunotherapy (AIT) is the only treatment that works on the causes of allergy. Available AIT nowadays are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for allergic rhinitis and asthma, while for allergy to Hymenoptera venom only subcutaneous route is recommended. A bulk of trials and meta-analyses demonstrated that efficacy and safety of AIT in decreasing allergic clinical symptoms and use of rescue medications, while its preventive capacity is yet under investigation. The most important of these effects is the prevention of potentially fatal anaphylactic reactions to Hymenoptera stings by venom immunotherapy (VIT). A certain number of studies thus far available showed that AIT, in both forms, is able to prevent the progress of allergic rhinitis into asthma and the development of new sensitizations. These effects should be related to the mechanisms of action of AIT. In fact, it has been demonstrated that both SCIT and SLIT are able to modify the allergen presentation by dendritic cells, with result in modification of the phenotype of allergen-specific T cells, switching from the typical of allergic inflammation Th2-type response to a Th1-type one. Also allergen-specific T regulatory (Treg) cells play a pivotal role by producing suppressive cytokines, such as IL-10 and TGF-beta. However, the only plain evidence of a preventive effect concerns VIT, while the other outcomes need to be furtherly investigated.

How to fit allergen immunotherapy in the elderly.

Asthma, allergic rhinitis (AR) and atopic dermatitis are very common in young people, but in the latest decades it was increasingly recognized that also individuals of higher ages, including the population over 65 years, are concerned. Actually, it is now acknowledged the aging does not considerably alter the immune response to allergens. Allergen immunotherapy (AIT) is the only treatment that works on the causes of allergy, but elderly people are commonly excluded from AIT, except the cases of insect sting allergy. A number of recent studies showed that aged individuals also successfully respond to AIT for respiratory allergy. Therefore, there is no reason to exclude elder patients from AIT. Anyhow, clinical conditions that are considered absolute or relative contraindications are quite frequent in this aged population, thus the risk/benefit ratio must be carefully evaluated for each patient, taking into account that the more frequent occurrence of co-morbidities and the consequent need of daily-based multidrug regimen can favor adverse effects. An important issue concern the ability of AIT, and particularly of sublingual immunotherapy, to significantly improve the quality of life, that often is particularly impaired in the elderly, reducing symptoms and drugs consumption.

Eosinophilic disorders of the gastro-intestinal tract: an update.

Eosinophilic diseases of the gastrointestinal tract, including eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), are rare chronic pathologies of the digestive system, with an immuno-mediated pathogenesis. Recent data suggest that, together with the "classic" IgE-response to allergens, also a delayed hypersensitivity mechanism could be involved in the development of eosinophilic disorders. EoE and EGE were studied only in the latest decades and as a consequence accurate data are not yet available, concerning not only pathogenesis, but also epidemiology, treatment and outcomes. The diagnosis of EoE is centered on endoscopic findings but the certainty is obtained by histological examination from biopsy samples, that has a sensitivity of 100% when based on five samples. The currently available treatments include topical corticosteroids, specific diets and endoscopic treatment. Concerning EGE, three subtypes (mucosal, muscular, and serosal) were identified. The diagnosis is based, as for EoE, on endoscopic and histological assessment, and the treatment includes pharmacological and dietetic approaches. Further studies are warranted in order to better define the etiology and pathogenesis of eosinophilic diseases of the gastrointestinal tract, and thus to develop more appropriate and specific therapies.

[Risk of pneumonia in patients with chronic obstructive pulmonary disease treated with inhaled corticosteroids: evidence and uncertainties]. / Il rischio di polmonite associato a terapia con corticosteroidi inalatori in pazienti con broncopneumopatia cronica ostruttiva: evidenze e incertezze.

A large number of studies, evaluated by several meta-analyses, indicate that patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids have a significantly increased risk of pneumonia which, however, is not associated with a corresponding increase in mortality. The increased risk seems to be exclusive of COPD, since meta-analyses involving patients with asthma treated with inhaled corticosteroids did not show a risk of pneumonia higher than that of the general population. Possible interventions to reduce this risk are to improve adherence to guidelines for prescribing inhaled corticosteroids in COPD (often used even in mild to moderate disease, for which they are not indicated), and using lower doses.

Assessing the Risk Factors for Refractory Eosinophilic Esophagitis in Children and Adults.

BACKGROUND: Up to one-third of the patients suffering from eosinophilic esophagitis (EoE) present a refractory form, as defined by nonresponsiveness in clinical, endoscopic, or histological assessment after first-line therapy. Several studies recently investigated which factors can influence the development of this disease, but very few analyzed the factors underlying refractory EoE. METHODS: Medical charts of patients affected by EoE were retrospectively evaluated. Phenotyping of patients was conducted according to demographic, clinical, histological, and treatment variables. Then, patients were divided into responder and nonresponder to therapy and distinguished among children and adults. RESULTS: Forty-five children and 35 adult EoE patients were included. In the pediatric population, female sex (p < 0.05) and a higher score of visual analogue scale (VAS) at the follow-up visit (p = 0.02) were significantly associated to the risk of refractory EoE. Among adults, statistical significance was reached for years of follow-up (p = 0.001), diagnostic delay (p = 0.03), use of antibiotics during infancy (p = 0.01), and food allergy (p = 0.04). CONCLUSIONS: Our study highlighted female sex and a higher VAS score at the time of follow-up visits as risk factors for refractory EoE in children, while the risk factors in adults were identified as fewer years of follow-up, greater diagnostic delay, use of antibiotics during infancy, and food allergy.

Sex in Respiratory and Skin Allergies.

A bulk of literature demonstrated that respiratory allergy, and especially asthma, is prevalent in males during childhood, while it becomes more frequent in females from adolescence, i.e., after menarche, to adulthood. The mechanisms underlying the difference between females and males are the effects on the immune response of female hormones and in particular the modulation of inflammatory response by estrogens, as well as the result of the activity of various cells, such as dendritic cells, innate lymphoid cells, Th1, Th2, T regulatory (Treg) and B regulatory (Bregs) cells, and a number of proteins and cytokines, which include interleukin (IL)-4, IL-5, IL-10, and IL-13. As far as sexual dimorphism is concerned, a gender difference in the expression profiles of histamine receptors and of mast cells was demonstrated in experimental studies. A critical phase of hormone production is the menstrual cycle, which often is associated with asthma deterioration, as assessed by worsening of clinical symptoms and increase of bronchial hyperresponsiveness. In asthmatic woman, there is a high risk to develop more severe asthma during menstruation. The higher prevalence of asthma in females is confirmed also in the post-menopause age, but the underlying mechanisms are not yet understood. In pregnancy, asthma may worsen but may also improve or remain unchanged, with no significant difference in frequency of these three outcomes. For allergic rhinitis, the available studies indicate, likewise asthma, a male predominance in prevalence in childhood that shifts to a female predominance in adolescence and adulthood, but further investigation is needed.

Efficacy and safety of honeybee and wasp tyrosine-adsorbed venom immunotherapy.

INTRODUCTION: It is acknowledged that any claim of efficacy of allergen immunotherapy must be done for each specific product, and this remains true also for venom immunotherapy (VIT). Thus, we evaluated the efficacy and safety of a specific tyrosine-adsorbed VIT for vespula spp. and honeybee in real-life. METHODS: Consecutive patients diagnosed with hymenoptera allergy, and receiving VIT for either vespula or honeybee with a tyrosine-adsorbed preparation were observed to evaluate the grade of reaction (according to Muller) at the first field re-sting. A modified ultra-rush protocol was used. RESULTS: A total of 247 patients (73 female) were observed (102 honeybee, group H, 145 vespula, group V). Seventy-five patients in group H had a re-sting, and 74/75 had a lower grade reaction at re-sting as compared to the pre-VIT reaction. Considering systemic reactions, protection was achieved in 89% of patients. In group V 118 patients were re-stung, and 76/118 patients with previous grade III-IV reaction had no more systemic reaction under VIT. Overall, considering systemic reactions, protection was achieved in 92% of subjects. Of note, in both groups there was a clear inverse correlation between the severity of pre-VIT and during VIT reactions. The duration of VIT at the time of re-sting did not affect the efficacy. The safety was overall good, with 18% ad 15.4% local reactions in groups H and V, respectively. DISCUSSION: Modified extracts, including tyrosine-absorbed, have the aim of improving the safety of VIT still yet maintaining the efficacy. Field re-sting is the best way to assess the efficacy in real life. In this observational study we could confirm the protective efficacy of the tyrosine-adsorbed extract, with a good safety expecially in the build-up using a modified-rush protocol. CONCLUSION: The tyrosine-adsorbed VIT used herein is a viable and advantageous form of treatment for hymenoptera allergy.

Allergen immunotherapy in atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic relapsing skin disease, characterized by flare-up due to the exposure to allergens in patients sensitized to them. Currently, therapy of AD is mainly based on symptomatic treatment and avoidance of irritating/allergenic factors, house dust mites being particularly important. Allergen immunotherapy (AIT) is suggested to be the only etiologic treatment, to modify the natural history of the disease. Areas covered: The aim of this review is investigating the putative role of AIT in AD through the evaluation of the most recent scientific literature. Several studies have been conducted since 1970, with promising results in improving the clinical outcome of AD, but they often lack the necessary scientific rigorousness. Moreover, heterogeneity of the studies makes it very difficult to compare and to analyze data in a systematic review or meta-analysis. Expert commentary: As a result of the above-mentioned limitations, the treatment of AD with causative aeroallergen can nowadays be suggested only as an add-on therapy in selected patients who are non-responsive to the traditional therapy.

Chronic Urticaria Patient Perspective (CUPP): The First Validated Tool for Assessing Quality of Life in Clinical Practice.

BACKGROUND: There is a need for validated tools to assess health-related quality of life (HRQoL) in routine clinical practice. OBJECTIVE: The aim of this study was to validate the Chronic Urticaria Patient Perspective (CUPP) for assessment of patients with chronic urticaria (CU) in clinical practice. METHODS: A provisional CUPP was developed from candidate items identified by following an iterative process in a retrospective analysis of 249 Chronic Urticaria Quality of Life Questionnaire questionnaires. The psychometric properties of the CUPP were then tested on a sample of patients enrolled in 13 Italian centers. RESULTS: The study population in the validation phase comprised 152 patients. The 10-item version of the CUPP showed satisfactory internal consistency (Cronbach's alpha values of 0.76 at visit 1 and 0.90 at visit 2), good criteria, and discriminative and convergent validity. Reliability was assessed in 34 patients with no changes in health (Global Rating Scale = 0 at visit 2) and was satisfactory (CCC [concordance correlation coefficient] = 0.9). Changes in CUPP scores were significantly associated with changes in Urticaria Activity Score (UAS)-Hive count (r = 0.36, P < .001), UAS-Itch severity (r = 0.48, P < .001), and UAS-Total score (r = 0.342, P < .001), all of which indicated good responsiveness. The minimal important difference was 1.5. CONCLUSIONS: CUPP is a simple 10-question tool with good psychometric properties that provides a valid, reliable, and standardized measurement of HRQoL in patients with CU.

Local allergic rhinitis: evolution of concepts.

The discovery of an exclusive local production of IgE antibodies dates back to the 1970s, but only recently the pathophysiology of such phenomenon was deeply investigated, leading to the concept of local allergic rhinitis (LAR). Currently, LAR is defined by the occurrence, in patients with symptoms clearly suggesting allergic rhinitis but with negative results to common allergy testing, of allergen specific IgE in the nasal mucosa. Most studies investigating LAR were based on the development of rhinitis symptoms following nasal provocation test (NPT) with the suspected allergens, but such test may be performed by a number of options, none of them being as yet acknowledged and recommended in consensus document. On the other hand, also the mere detection of IgE in the nasal mucosa indicates, as for IgE measurement in blood or other tissues, allergic sensitization but cannot give the certainty of clinical allergy. Therefore, the combination of IgE detection in nasal mucosa and a positive result of NPT should be used to diagnose LAR. Recent data on the use for in vitro testing of molecular allergy diagnostics in place of whole allergen extracts suggest that this method could improve the sensitivity and specificity of laboratory tests, and an appraisal of the basophil activation test as a third level technique, to be implemented when the results of local IgE testing and NPT are uncertain, is currently ongoing.

Scombroid syndrome: it seems to be fish allergy but... it isn't.

PURPOSE OF REVIEW: Scombroid poisoning is a frequent cause of admission in emergency department. In everyday clinical practice, it can be difficult to discriminate between scombroid syndrome and fish allergy. The aim of this review is to provide the clinician some instruments to make a correct differential diagnosis. RECENT FINDINGS: In the last few years, a better characterization of scombroid syndrome occurred, in particular regarding its possible severe presentations. Two cases of Kounis syndrome secondary to scombroid syndrome have been described and in these cases a differential diagnosis in patients with this clinical presentation can be even more difficult. Finally, in term of diagnosis, the useful role of serum tryptase was recently consolidated. SUMMARY: Scombroid syndrome is a histamine-induced reaction because of the ingestion of histamine-contaminated fish, whereas fish allergy is an IgE-mediated reaction. Clinical presentation can be similar and for this reason scombroid syndrome is often misdiagnosed. The differences lie in pathogenic mechanisms, possible outcome, therapy, and prevention measures. Moreover, some laboratory tests are helpful to discriminate between the two diseases.