Highlights and recent developments in allergic diseases in EAACI journals (2019).

The European Academy of Allergy and Clinical Immunology (EAACI) owns three journals: Allergy, Pediatric Allergy and Immunology and Clinical and Translational Allergy. One of the major goals of EAACI is to support health promotion in which prevention of allergy and asthma plays a critical role and to disseminate the knowledge of allergy to all stakeholders including the EAACI junior members. There was substantial progress in 2019 in the identification of basic mechanisms of allergic and respiratory disease and the translation of these mechanisms into clinics. Better understanding of molecular and cellular mechanisms, efforts for the development of biomarkers for disease prediction, novel prevention and intervention studies, elucidation of mechanisms of multimorbidities, entrance of new drugs in the clinics as well as recently completed phase three clinical studies and publication of a large number of allergen immunotherapy studies and meta-analyses have been the highlights of the last year.

Correction to: Highlights and recent developments in skin allergy and related diseases in EAACI journals (2018).

[This corrects the article DOI: 10.1186/s13601-019-0299-y.].

Highlights and recent developments in skin allergy and related diseases in EAACI journals (2018).

The European Academy of Allergy and Clinical Immunology (EAACI) supports three journals: Allergy, Paediatric Allergy and Immunology as well as Clinical and Translational Allergy. The major goals of EAACI include (i) supporting health promotion in which the prevention of allergy and asthma plays a critical role and (ii) disseminating the knowledge of allergy to all stakeholders including the EAACI junior members. Substantial progress was made in 2018 in the identification of basic mechanisms of atopic dermatitis and urticaria and the translation of these mechanisms into clinics. Many large epidemiologic studies and meta-analyses have been the highlights of the last year.

How to manage chronic urticaria 'beyond' guidelines: a practical algorithm.

Chronic urticaria (CU) is a disease characterized by pruritic weals, angio-oedema or both occurring for at least 6 weeks. It encompasses spontaneous and inducible urticarias. The national and international guidelines outline the principles of treatment. Omalizumab, an anti-immunoglobulin E monoclonal antibody, has transformed the management of many severe and treatment-refractory patients. However, current UK guidance on its use does not address the needs of those with less severe disease, inducible urticarias, idiopathic histaminergic angio-oedema without weals as a presentation of CU and omalizumab non-responders. Our algorithm and a summary of the evidence to support its principles offers guidance and a more systematic targeted approach to using a range of 'off-label' agents for specific phenotypes of CU. It will be of use when guideline-recommended mast cell mediator antagonists fail to control symptoms and/or using omalizumab is ineffective, not practical or unfunded.

Definition, aims, and implementation of GA(2) LEN Urticaria Centers of Reference and Excellence.

BACKGROUND: GA²LEN, the Global Allergy and Asthma European Network, has recently launched a program for the development, interaction, and accreditation of centers of reference and excellence in special areas of allergy embedded in its overall quality management of allergy centers of excellence. The first area chosen is urticaria. Urticaria is a common and debilitating condition and can be a challenge for both patients and treating physicians, especially when chronic. Centers of reference and excellence in urticaria (UCAREs) can help to improve the management of hard-to-treat conditions such as urticaria. AIMS: Here, we describe the aims, the requirements and deliverables, the application process, and the audit and accreditation protocol for GA²LEN UCAREs. RESULTS: The main aims of GA²LEN UCAREs are to provide excellence in urticaria management, to increase the knowledge of urticaria by research and education, and to promote the awareness of urticaria by advocacy activities. To become a certified GA²LEN UCARE, urticaria centers have to apply and fulfill 32 requirements, defined by specific deliverables that are assessed during an audit visit. DISCUSSION AND CONCLUSION: The GA²LEN UCARE program will result in a strong network of urticaria specialists, promote urticaria research, and harmonize and improve urticaria management globally.

The definition, diagnostic testing, and management of chronic inducible urticarias - The EAACI/GA(2) LEN/EDF/UNEV consensus recommendations 2016 update and revision.

These recommendations for the definition, diagnosis and management of chronic inducible urticaria (CIndU) extend, revise and update our previous consensus report on physical urticarias and cholinergic urticaria (Allergy, 2009). The aim of these recommendations is to improve the diagnosis and management of patients with CIndU. Our recommendations acknowledge the latest changes in our understanding of CIndU, and the available therapeutic options, as well as the development of novel diagnostic tools.

Unexplained recurrent fever: when is autoinflammation the explanation?

Recurrent fever can be the sole or leading manifestation of a variety of diseases including malignancies, autoimmune diseases and infections. Because the differential diagnoses are manifold, no formal guidelines for the approach of patients with recurrent fever exists. The newly recognized group of autoinflammatory diseases are often accompanied by repetitive fever attacks. As these episodes are frequently associated by a variety of divergent presentations, the differentiation of other causes for febrile illnesses can be difficult. In this article, we first review disease entities, which frequently present with the symptom of recurrent fever. In a next step, we summarize their characteristic pattern of disease presentation. Finally, we analyse key features of autoinflammatory diseases, which are helpful to distinguish this group of diseases from the other causes of recurrent fever. Recognizing these symptom patterns can provide the crucial clues and, thus, lead to the initiation of targeted specific diagnostic tests and therapies.

EAACI taskforce position paper: evidence for autoimmune urticaria and proposal for defining diagnostic criteria.

An autoimmune subset of chronic spontaneous urticaria is increasingly being recognized internationally, based on laboratory and clinical evidence that has accrued over the last 20 years. This evidence has been reviewed by a taskforce of the Dermatology section of the European Academy of Allergy and Clinical Immunology. Functional autoantibodies in chronic urticaria (CU) patient sera have been demonstrated against IgE and FcεRIα by basophil and mast cell histamine release assays and by basophil activation assays. Antibody specificity has been confirmed by immunoassay, but there is a poor correlation between functionality and immunoreactivity. Approximately 25% of CU patients have a positive basophil histamine release assay and show autoreactivity (a positive autologous serum skin test), whereas 50% are negative regarding both. Functionality of CU sera appears to be complement dependent on mast cells but not exclusively on basophils. Basophil activation by CU sera is predominantly restricted to IgG1 and IgG3 subclasses. Circumstantial evidence for CU being an autoimmune disease comes from an observed association with other autoimmune diseases, a strong association between serum functionality and HLA-DR4 haplotype and the good response of CU patients to immunotherapies. It was proposed that a study should be undertaken to prospectively validate potentially relevant clinical criteria (from the history, examination and routinely available clinical investigations) against a new 'gold standard' for the diagnosis of ACU (positive autoreactivity, functional bioassay and immunoassay) to define preliminary criteria sets for the diagnosis of ACU based on clinical and laboratory features with highest individual sensitivity and specificity.

How not to miss autoinflammatory diseases masquerading as urticaria.

Urticarial skin reactions are one of the most frequent problems seen by allergists and clinical immunologists in daily practice. The most common reason for recurrent wheals is spontaneous urticaria. There are, however, several less common diseases that present with urticarial rash, such as urticarial vasculitis and autoinflammatory disorders. The latter include cryopyrin-associated periodic syndrome and Schnitzler's syndrome, both rare and disabling conditions mediated by increased interleukin-1 secretion. Apart from the urticarial rash, patients are suffering from a variety of systemic symptoms including recurrent fever attacks, arthralgia or arthritis and fatigue. Autoinflammatory diseases are often associated with a diagnostic delay of many years and do not respond to antihistamines and other treatments of urticaria. Also, the chronic inflammation may lead to long-term complications such as amyloidosis. It is therefore important not to miss these diseases when diagnosing and treating patients with chronic recurrent urticarial rash. Here, we present clinical clues and tips that can help to identify autoinflammatory disorders in patients presenting with chronic urticarial rash and discuss their clinical picture and management.

Unmet clinical needs in chronic spontaneous urticaria. A GA²LEN task force report.

Chronic spontaneous urticaria, formerly also known as chronic idiopathic urticaria and chronic urticaria (CU), is more common than previously thought. At any time, 0.5-1% of the population suffers from the disease (point prevalence). Although all age groups can be affected, the peak incidence is seen between 20 and 40 years of age. The duration of the disease is generally 1-5 years but is likely to be longer in more severe cases, cases with concurrent angioedema, in combination with physical urticaria or with a positive autologous serum skin test (autoreactivity). Chronic spontaneous urticaria has major detrimental effects on quality of life, with sleep deprivation and psychiatric comorbidity being frequent. It also has a large impact on society in terms of direct and indirect health care costs as well as reduced performance at work and in private life. In the majority of patients, an underlying cause cannot be identified making a causal and/or curative treatment difficult. Nonsedating H1-antihistamines are the mainstay of symptomatic therapy, but treatment with licensed doses relieves symptoms effectively in < 50% of patients. Although guideline-recommended updosing up to fourfold increases symptom control in many patients, a substantial number of patients have only little benefit from H1 -antihistamines. Consequently, there is a great need for new therapeutic strategies.

Serum total tryptase levels are increased in patients with active chronic urticaria.

BACKGROUND: We have demonstrated previously mast cell histamine release upon incubation with chronic urticaria (CU) sera, presumably by degranulation. OBJECTIVE: To explore total and mature tryptase in order to assess whether any increase in total tryptase levels is due in part to mast cell degranulation or to mast cell burden. We also wanted to explore differences between the autoimmune groups called idiopathic (serum unable to activate basophils), and to correlate total and mature tryptase levels with different urticaria features. METHODS: We measured total and mature tryptase serum levels in 81 CU patients, 16 atopic donors and 21 healthy control sera. We assessed autoimmunity by measuring the CD63 expression in normal basophil donors upon incubation with CU sera. RESULTS: We found significantly higher levels of total tryptase in the sera of CU patients (6.6 ±4.1 µg/L) than in sera from healthy non-atopic subjects (4.4 ±2.8 µg/L) and from atopic subjects (4.5 ±1.7 µg/L). Mature tryptase levels were undetectable (<1 ng/mL). Total tryptase levels in the autoimmune urticaria group were significantly higher (9.8 ±5.4 µg/L) than the idiopathic urticaria group (4.4 ±2.2 µg/L). A significant difference in total tryptase was found between symptomatic patients (7.3 ±4.1 µg/L) compared with asymptomatic ones (5.7 ±4.1 µg/L) at the time of venesection. No difference was found in mature tryptase levels either. CONCLUSION: Total elevated tryptase levels are not accompanied by an elevated mature tryptase levels, as might be expected if the serum levels reflected mast cell degranulation.