Anaphylaxis still represents a global challenge, not only for allergists, in terms of both practical management and pathophysiological insights.
Although anaphylaxis has been recognized for a long time as a model of type I-IgE/non-IgE, mast cell/basophil-mediated hypersensitivity, the results of the latest investigations on its mechanisms have revealed an unexpected complexity regarding, mediators, co-factors and risk factors [1,2]. Such findings have important implications on the management of anaphylaxis, paving the way to prevention strategies in addition to allergen avoidance and to a personalized approach . Under that perspective, the individual risk assessment and management plan should be tailored by taking into account patient-related and, environmental determinants.
Whenever exploring the pathophysiological picture underlying the clinical manifestations of anaphylaxis, an increasing amount of evidence confirms and enriches the central role of mast cells and their mediators . Mast cells act both as major players of the anaphylaxis cascade with the triggered release of mediators responsible for the clinical symptoms, and as a cause of recurrent ‘idiopathic’ unprovoked anaphylaxis, in the context of the broad spectrum of clonal and nonclonal mast cell disorders. As an example, the recently described new subgroup of indolent systemic mastocytosis without skin lesions (ISMs), characterized by a low bone marrow mast cell load and a low risk for disease progression, which is more frequent in men and associated with hymenoptera venom anaphylaxis . This form of anaphylaxis can be targeted with specific venom immunotherapy, which prevents recurrent life-threatening episodes .
Measurement of serum tryptase levels (STLs) can be used to support the clinical diagnosis of systemic anaphylaxis; in particular, blood samples should be collected within 1–2 h from the appearance of the initial clinical symptoms and after 24–48 h in order to evaluate a significant difference. An increase over 11.4 ng/ml or an increase of baselineX1.2+ 2 ng is indicative of mast cell/basophil activation and mediators’ release. However, despite the established relevance of triptase, it is still widely under-utilized, leading to the underdiagnosis of anaphylaxis and the delay in its treatment .
Regarding patient-related determinants, recent evidence has highlighted the importance of sex, age and comorbidities.
In females, hormonal status and the X-chromosome coded factors heavily impact on the regulation of T-cell and B-cell responses, accounting for the sex differences in prevalence and clinical presentation of autoimmunity and atopy. Most of the research has been in rodents, in which anaphylaxis is more prevalent in females, and associated with oestrogen-induced increases in eNOS and mast cell degranulation with increased vascular permeability and cardiovascular collapse. In humans, the appearance of catamenial and peripartum anaphylaxis suggests the role of sex hormones in the pathophysiology of anaphylaxis and while oestrogens and progesterone have been shown to affect mast cells in vitro, their in-vivo role is still unknown .
The burden of anaphylaxis is increasing in all age groups, but its impact in terms of morbidity and mortality is much higher in adolescents. Due to a complex interaction of psychosocial factors, adolescents are more prone to risk-taking behaviours, to poor judgement during reactions and to low compliance with management and treatment recommendations. Age should be considered a specific risk factor, and a carefully tailored approach is required to overcome the potential barriers to improve the safety during the management and treatment of anaphylaxis in certain age groups .
Poor asthma control is associated with more severe anaphylaxis reactions, and in children, with more recurrent episodes. Asthma control in patients suffering from anaphylaxis is recommended before procedures including provocation tests or desensitization .
The number of potential triggers associated to anaphylaxis has dramatically increased recently, associated to the introduction of new drugs, global climate changes and new environmental exposures .
New biologics drugs, small molecules and monoclonal antibodies, represent a true revolution not only in the treatment of oncologic and inflammatory diseases but also in terms of new potentially allergenic compounds. In addition to the traditional IgE-mediated reactions, biological agents are able to trigger cytokine release reactions, because of their immunological activity . Monoclonal antibodies (mAb), such as with anti-IgE activity, have also been used to prevent/treat anaphylactic reactions, in particular, anaphylaxis associated with allergen immunotherapy, management of food allergy, idiopathic anaphylaxis, and mast cell clonal and nonclonal disorders .
Global climate change has contributed to the redistribution of stinging insects around the world. The trend of insect venom hypersensitivity reactions is changing accordingly, and requires to be considered in the anaphylaxis diagnostic work-up .
Globalization promotes the worldwide circulation of food and products leading to substantial modifications in terms of allergen exposure in the different countries. Globalization also sustains the availability of a huge amount of information through Internet. Looking at the so-called ‘Google trends’, it appears quite clear that patients seek more awareness about their disease, its causes and available treatments . It suggests and somehow confirms that anaphylaxis significantly affects the quality of life of patients, and reveals that their expectations about anaphylaxis management are poorly satisfied. On the other hand, web consulting entails, the risk for sources of inaccurate or wrong information. It may impact not only on patient's education but also on healthcare worker's practice. Scientific Societies worldwide should work on providing lists of reliable web sources for patients and physician who are interested in the topic; some suggestions are already available .
Anaphylaxis still represents a challenge, underdiagnosed and undertreated, because of its potential life-threatening consequences when epinephrine is not used promptly. In fact, its optimal management requires that allergists keep following both the scientific advances but also more in general the global changes potentially impacting on the burden of the disease. In order to achieve the optimal management, collaboration strategies between scientific societies worldwide and integrated action plan for prevention and treatment are mandatory for the best practice in the allergy field .
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