Molecular aspects of allergens in atopic dermatitis

imagePurpose of review: Molecular allergology uses pure, mainly recombinant and structurally defined allergen molecules and allergen-derived epitopes to study mechanisms of IgE-associated allergy, to diagnose, and even predict the development of allergic manifestations and to treat and prevent IgE-associated allergies. Atopic dermatitis, a chronic inflammatory skin disease is almost always associated with IgE sensitization to allergens. However, also non-IgE-mediated pathomechanisms seem to be operative in atopic dermatitis and it is often difficult to identify the disease-causing allergens. Here we review recent work showing the usefulness of molecular allergology to study mechanisms of atopic dermatitis, for diagnosis and eventually for treatment and prevention of atopic dermatitis.

Recent findings: IgE sensitization to airborne, food-derived, microbial allergens, and autoallergens has been found to be associated with atopic dermatitis. Using defined allergen molecules and non-IgE-reactive allergen derivatives, evidence could be provided for the existence of IgE- and non-IgE-mediated mechanisms of inflammation in atopic dermatitis. Furthermore, effects of epicutaneous allergen administration on systemic allergen-specific immune responses have been studied. Multi-allergen tests containing micro-arrayed allergen molecules have been shown to be useful for the identification of culprit allergens in atopic dermatitis and may improve the management of atopic dermatitis by allergen-specific immunotherapy, allergen avoidance, and IgE-targeting therapies in a personalized medicine approach.

Summary: Molecular allergology allows for dissection of the pathomechanisms of atopic dermatitis, provides new forms of allergy diagnosis for identification of disease-causing allergens, and opens the door to new forms of management by allergen-specific and T cells-targeting or IgE-targeting interventions in a personalized medicine approach.

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Allergen immunotherapy for the treatment of respiratory allergies in the elderly

imagePurpose of review: Respiratory allergies, including asthma and allergic rhinitis can also occur in the elderly. Allergen immunotherapy for allergic diseases is the only disease-modifying treatment for patients with allergies available thus far. Here, we review current evidence supporting the use of allergen immunotherapy in the elderly and discuss its efficacy and utility for the treatment of respiratory allergic diseases in this setting.

Recent findings: Subcutaneous and/or sublingual immunotherapy are effective therapeutic options in not only young but also older patients. Allergen immunotherapy reduces medication and symptom scores in the elderly and can thus be safely prescribed in this population.

Summary: Elderly individuals with proven, clinically relevant immunoglobulin E sensitization to inhalant allergens may benefit from allergen immunotherapy for respiratory allergic diseases. Older patients without contraindications should therefore be considered for treatment, with the additional benefit of reduced medication and symptom scores.

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Hypersensitivity reactions to gadolinium-based contrast agents

imagePurpose of review: Gadolinium-based contrast agents (GBCAs) have been utilized since the late 1980s to enhance the diagnostic value of MRI studies. They are known to have excellent safety profile and serious adverse reactions are uncommon despite widespread global use. However, immediate hypersensitivity reactions are well described in the literature, with urticaria the most common manifestation. Anaphylaxis can occur, though fatality is extremely rare. This review explores the incidence of GBCA-related hypersensitivity reactions and highlights potential risk factors.

Recent findings: Emerging evidence suggests that immediate hypersensitivity reactions to GBCAs can be IgE-mediated. Skin testing may be informative in confirmation of causality and revealing cross-reactivity patterns.

Summary: GBCA hypersensitivity is infrequent but can be serious. Familiarity with management of acute hypersensitivity reactions may be lifesaving. Appropriate use of diagnostic testing can be used to guide future management of patients who have suffered from such reactions.

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Seasonal Allergic Rhinitis: A focused systematic review and practice parameter update

imagePurpose of review: The review compares and contrasts seven major United States and international allergic rhinitis guidelines from 2008 to 2017.

Recent findings: Despite many treatment options for allergic rhinitis, patients often report lack of therapeutic control and a reduced quality of life. Guidelines intended to improve allergic rhinitis care have been evolving into evidence based, systematic reviews, with less reliance on consensus of expert opinion characteristic of more traditional guidelines. The first Grading of Recommendations Assessment, Development, and Evaluation-based guideline developed in the United States for seasonal allergic rhinitis was first published in 2017.

Summary: When critically analyzing the allergic rhinitis guidelines that use the rigorous Grading of Recommendations Assessment, Development, and Evaluation methodology, different groups of expert authors, using the same reference articles, will, at times, reach different conclusions regarding the quality of the evidence and the strength of the recommendation. Factors potentially contributing to these divergent determinations include: lack of objective primary outcome measures in allergic rhinitis, poorly defined Minimal Clinically Important Difference, failure to include all interested parties in guideline development, for example, patients, and subjectivity inherent in the expert panel.

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Aspirin challenge and desensitization: how, when and why

imagePurpose of review: To investigate the current approach to aspirin challenge (drug provocation) and/or desensitization in patients with histories of hypersensitivity reactions to it, particularly in those with cardiovascular diseases.

Recent findings: The literature indicates that patients with coronary artery disease (CAD), including those with an acute coronary syndrome, may safely undergo low-dose aspirin challenge and/or desensitization. Recently, flowcharts regarding challenge/desensitization procedures with aspirin in patients with CAD and histories of aspirin hypersensitivity reactions have become available. Aspirin desensitization and continuous aspirin therapy constitute an effective option in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory diseases (NERD) who have suboptimally controlled asthma or rhinosinusitis, or require multiple revision polypectomies.

Summary: The use of aspirin has proven to reduce morbidity and mortality associated with CAD. There is a general consensus on aspirin’s effectiveness in secondary prevention of CAD. Therefore, aspirin desensitization is necessary in patients with CAD and histories of hypersensitivity reactions to it. The effectiveness of aspirin desensitization and continuous therapy in patients with NERD has been shown in numerous studies. However, shared selection criteria of candidates for aspirin challenge/desensitization procedures, and simple and homogeneous protocols are necessary. Moreover, preventive safety measures are still needed in order to reduce the potential risks of these procedures.

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Reactions to cytostatic agents in children

imagePurpose of review: The current review will focus on drug hypersensitivity reactions to chemotherapy specifically to those drugs most used in children. We know that potentially all chemotherapeutic agents can cause infusion reactions, generally defined as adverse drug reactions. Of these, some are Type A, defined as expected and described in the characteristics of the drug and others, and Type B, defined as unexpected reactions which cannot be explained by the known toxicity profile of the drug. When an unexpected reaction occurs, drugs we can refer as hypersensitivity reactions (HSRs). Some of these (HSRs) are allergic reactions as they have an underlying immunologic mechanism. In general, the cytotoxic agents most commonly associated with HSRs are the platinum salts derivatives, taxanes, pegylated liposomal doxorubicin, L-asparaginase, procarbazine, etoposide, bleomycin, and cytarabin.

Recent findings: HSRs may also occur in children with cancer, during the treatment with chemotherapeutic drugs. The most used drugs of this group in children to cause HSRs are: carboplatin, L-asparaginase, and methothrexate. The aim of this review is to summarize the incidence and the clinical features of HSRs occurring with these drugs in children.

Summary: The aim of this review is to summarize the incidence and the clinical features of HSRs occurring with these drugs in children. The current review will focus on the most involved drugs in children, the type of reactions, the mechanisms involved, and the best way to manage them.

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Alternative treatments for chronic spontaneous urticaria beyond the guideline algorithm

imagePurpose of review: The international EAACI/GA2LEN/EDF/WAO guideline suggests a stepwise approach for the therapeutic management of chronic spontaneous urticaria (CSU), outlined in an algorithm. The aim of this article is to summarize and review the evidence available on alternative treatment options for CSU outside of this algorithm.

Recent findings: Although CSU is a common disease, there are a limited number of high-quality studies, and only antihistamines and omalizumab are licensed for its treatment. Most studies regarding alternative therapies for CSU show methodological limitations and a high risk of bias. For many therapies, only case reports and uncontrolled studies exist. Recent publications on alternative treatments for chronic urticaria/CSU include reports on the use of adalimumab, rituximab, vitamin D, probiotics, histaglobulin, injection of autologous whole blood or serum, and phototherapy.

Summary: Numerous treatments beyond the guideline algorithm have been evaluated in patients with refractory CSU. The global level of evidence to support their efficacy in CSU is low or very low. Further research is needed to assess the efficacy and safety of alternative therapies of CSU to manage adequately those patients who do not respond to the treatments included in the algorithm.

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