Irene Martignago

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

Purpose of reviewScombroid 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 findingsIn 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. SummaryScombroid 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.

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.

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.

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.

Importance of hypersensitivity in adverse reactions to drugs in the elderly

BackgroundThe 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.ObjectiveThe 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.MethodsWe 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.ResultsOut 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.ConclusionsHDR 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.

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.

Allergic rhinitis: pharmacotherapy in pregnancy and old age

ABSTRACT Introduction: Allergic rhinitis (AR) affects 20-30% of women in reproductive age and may worsen during pregnancy. About 10% of the elderly suffer from AR, and it could be under-diagnosed in these patients. Many drugs are currently available, however AR treatment during pregnancy and old age represents a challenging issue. Areas covered: A review of the literature on the topic has been performed. Expert commentary: In pregnancy, drug avoidance should be carefully balanced with the need for AR optimal control. Topical drugs are suggested as a first approach. The safety and tolerability profile of second-generation antihistamines is well supported. If allergen immunotherapy (AIT) is ongoing and well tolerated, there is no reason for stopping it. AIT initiation in pregnancy is not recommended. For elderly patients, no specific concerns have been highlighted regarding topical treatments, except from nasal decongestionants. Second generation antihistamines are generally well tolerated. Old age should not preclude AIT.

Allergen immunotherapy in atopic dermatitis

ABSTRACT 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.

Use of a Combination of Allergen Immunotherapy and Omalizumab for Prevention of Anaphylaxis

Purpose of reviewAllergen immunotherapy (AIT) is aimed at the etiological treatment of respiratory allergy and Hymenoptera venom allergy, while it is still under investigation for food allergy. The incidence of anaphylactic reactions to AIT is generally low, but may hamper its completion and makes needed preventive treatment.Recent findingsSeveral studies focused the attention on the use of the anti-IgE antibody omalizumab to prevent anaphylaxis in patients at high risk of systemic reactions, that is especially elevated during food allergy AIT and, in certain circumstances, during venom immunotherapy (VIT).SummaryWe performed a systematic review to analyze the use of omalizumab to prevent anaphylaxis during the course of AIT. The administration of omalizumab prior to AIT proved to improve the safety, reducing the rate of systemic adverse reactions. Double-blind placebo-controlled trials are rare and most of the available studies are case/small series reports. Further studies are needed to demonstrate the indication of omalizumab treatment in AIT.

Can the Pattern of Early Sensitization to Allergen Molecules Drive a New Approach for Prevention of Allergy

https://doi.org/10.1016/j.ebiom.2017.11.016 2352-3964/© 2017 The Author(s). Published by Elsevier B Identifying the causative agent is a major aim of diagnostic work-up any allergic symptom of rhinitis, asthma or eczema by questionnaires. for allergy. However, a positive result from skin tests or in vitro specific IgE measurement indicates sensitization but not necessarily clinical allergy. In fact, it is quite common to see a patient with positive tests to pollens with no respiratory symptoms during the specific flowering seasons of such pollens. Using as example the most recent study, 53.5% of 501 unselected subjects aged 12–21 years fromAustria showed IgE reactivity to at least one allergen, with the highest rate for grass pollen, dust mites, birch pollen and cat, but only 21.9% had a diagnosed allergy (Stemeseder et al., 2017). Among the different hypotheses on the immunological mechanisms underlying asymptomatic sensitization, some issues, as reviewed by Bodtger in 2004, were apparent to characterize asymptomatic sensitization (Bodtger, 2004). They included the lack of a late-phase reaction and of eosinophil stimulation and migration in response to allergen challenge, and low levels of interleukin (IL)-5, that is themajor cytokine responsible for activation, proliferation and survival of eosinophils. A role for allergen avoidance was suggested to be successful in reducing development of allergy (Bodtger, 2004). Actually, in a study assessing during 5 years the longitudinal sensitization to 6 aeroallergens in 828 children aged 6–11 years living in the semiarid US southwest, new allergen sensitizations were detected in 30.2%. Also remittance from positive to negative tests was observed, mostly concerning seasonal allergens (Stern et al., 2004). In recent years, the introduction of molecular diagnostics, by which specific IgE (sIgE) to single allergen molecules are measured, was a significant advance not only for diagnosis of allergy but also for investigating epidemiologic and natural history aspects (Matricardi et al., 2016). In the present issue of the Journal, Wickman et al. report the results of a study on IgE reactivity to 132 allergen molecules in a population based birth cohort of children from Sweden and in birth cohort of children from U.K. (Wickman et al., n.d.) The Swedish cohort included a random sample of 786 children (from the original number of 4089). At the age of 4, 8 and 16 years IgE reactivity was analyzed, along with the collection of