Anna Sala-Cunill

Usefulness and limitations of sequential serum tryptase for the diagnosis of anaphylaxis in 102 patients.

Background: The diagnosis of anaphylaxis is based on clinical history since no reliable biological marker is currently available to confirm the diagnosis. Objective: It was the aim of this study to determine sequential serum tryptase concentrations during anaphylaxis and to evaluate its potential as a diagnostic marker. Methods: We performed a prospective study including patients with acute anaphylaxis (according to the National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network criteria) attending the emergency department. Demographic characteristics, anaphylactic triggers, specific risk factors, clinical characteristics and management of anaphylaxis were recorded. Serum tryptase was measured at 1–2 h (T1), 4–6 h (T2) and 12–24 h (T3) following onset of the episode and at basal conditions (TB). Results: A total of 102 patients were included (63 females, mean age 47.4 ± 19.1 years). Tryptase concentration at T1 (19.3 ± 15.4 µg/l) was significantly higher than at T2, T3 and TB (all <11.4 µg/l; p < 0.0001). Importantly, tryptase was not raised in 36.3% of cases; furthermore, in 60.6% of these patients, no changes were observed in tryptase levels comparing T1 and TB (ΔT1–TB = 0). Tryptase was more frequently elevated in more severe anaphylaxis (p < 0.0001) and positively correlated with the grades of severity (p < 0.001, r = 0.49). Anaphylaxis was more severe and tryptase concentration higher when the causative agent was a drug compared to food, both at T1 (p = 0.045) and at TB (p = 0.019). Age and coronary risk factors were associated with more severe anaphylaxis (p = 0.001). Conclusion: Tryptase is a biomarker related to the severity of anaphylaxis. However, since its concentration remains unaltered in a considerable number of patients during acute anaphylaxis, there is a need for more reliable diagnostic biological tests.

Hereditary angioedema: a bradykinin-mediated swelling disorder

Edema is tissue swelling and is a common symptom in a variety of diseases. Edema form due to accumulation of fluids, either through reduced drainage or increased vascular permeability. There are multiple vascular signalling pathways that regulate vessel permeability. An important mediator that increases vascular leak is the peptide hormone bradykinin, which is the principal agent in the swelling disorder hereditary angioedema. The disease is autosomal dominant inherited and presents clinically with recurrent episodes of acute swelling that can be life-threatening involving the skin, the oropharyngeal, laryngeal, and gastrointestinal mucosa. Three different types of hereditary angiodema exist in patients. The review summarises current knowledge on the pathophysiology of hereditary angiodema and focuses on recent experimental and pharmacological findings that have led to a better understanding and new treatments for the disease.

Allergic diseases in the elderly.

Demographic distribution of the population is progressively changing with the proportion of elderly persons increasing in most societies. This entails that there is a need to evaluate the impact of common diseases, such as asthma and other allergic conditions, in this age segment. Frailty, comorbidities and polymedication are some of the factors that condition management in geriatric patients. The objective of this review is to highlight the characteristics of allergic diseases in older age groups, from the influence of immunosenescence, to particular clinical implications and management issues, such as drug interactions or age-related side effects.

Biomarkers of anaphylaxis, beyond tryptase.

Purpose of reviewThe purpose of this study is to describe the current knowledge regarding mediators involved in anaphylactic reactions, with a special focus on key effector cells and mechanisms. Recent findingsNew insight into the potential relevance of pathways other than mast cell degranulation has been unravelled, such as the role of cytokines, platelet activation factor, lipid mediators and their metabolism or the activation of the contact system. SummaryGaining knowledge into these pathophysiologic mechanisms will allow researchers to pursue the identification of risk factors and new preventive and therapeutic strategies in anaphylaxis.

The Mast Cell, Contact, and Coagulation System Connection in Anaphylaxis

Anaphylaxis is the most severe form of allergic reaction, resulting from the effect of mediators and chemotactic substances released by activated cells. Mast cells and basophils are considered key players in IgE-mediated human anaphylaxis. Beyond IgE-mediated activation of mast cells/basophils, further mechanisms are involved in the occurrence of anaphylaxis. New insights into the potential relevance of pathways other than mast cell and basophil degranulation have been unraveled, such as the activation of the contact and the coagulation systems. Mast cell heparin released upon activation provides negatively charged surfaces for factor XII (FXII) binding and auto-activation. Activated FXII, the initiating serine protease in both the contact and the intrinsic coagulation system, activates factor XI and prekallikrein, respectively. FXII-mediated bradykinin (BK) formation has been proven in the human plasma of anaphylactic patients as well as in experimental models of anaphylaxis. Moreover, the severity of anaphylaxis is correlated with the increase in plasma heparin, BK formation and the intensity of contact system activation. FXII also activates plasminogen in the fibrinolysis system. Mast cell tryptase has been shown to participate in fibrinolysis through plasmin activation and by facilitating the degradation of fibrinogen. Some usual clinical manifestations in anaphylaxis, such as angioedema or hypotension, or other less common, such as metrorrhagia, may be explained by the direct effect of the activation of the coagulation and contact system driven by mast cell mediators.

The Role of Mast Cells Mediators in Angioedema Without Wheals

Opinion statementAngioedema is defined as localized and transient edema of the deep skin layers or the upper respiratory or gastrointestinal mucosa. Although the most common sites of involvement are the tongue, lips, face, and throat, angioedema may also occur in the extremities, genitalia, and viscera, and it can be life-threatening when affecting the upper airway. Angioedema is due to a temporary increase of the vascular permeability caused by vasoactive mediators. However, the mechanisms and the mediators involved in angioedema without wheals vary depending on the type of angioedema. The purpose of this review is to give new insights on angioedema without wheals. To facilitate the understanding of the different types of angioedema, a modified classification of angioedema without wheals from the Hereditary Angioedema International Working Group consensus is proposed. It also summarizes the pathophysiology of the main types of AE and describes the current knowledge regarding the role of the mast cell mediators involved. Finally, given that the treatment of angioedema has changed greatly in the last years, this review also describes the specific treatment options of angioedema without wheals. Gaining knowledge into these pathophysiologic mechanisms of angioedema and into the gaps in the diagnosis will allow to improve the management of these patients, avoiding fatal outcomes. Key points: - Angioedema is a localized, self-limiting, no pitting swelling that can be life-threatening and needs adequate treatment to avoid fatal outcomes.- The mechanisms and the mediators involved in angioedema without wheals may vary depending on the type of angioedema; therefore, it is important to understand the physiopathology of each type of angioedema to improve the differential diagnoses.- There is a need to develop standardized diagnostic tests to differentiate types of angioedema in order to improve management.