The Chronic Urticaria Registry: rationale, methods and initial implementation.

BACKGROUND: Chronic urticaria (CU) is a common disease, characterized by the recurrent appearance of wheals, angioedema or both for more than 6 weeks. Its underlying biology is not well understood, and many patients do not obtain sufficient relief from recommended treatments. Patient registries are rapidly growing as a form of research, because they can provide powerful, data-driven insights about the epidemiology of diseases, real-world effectiveness of treatments, rare patient types, safety monitoring, healthcare costs and opportunities for quality improvement of healthcare delivery. OBJECTIVES: The Chronic Urticaria Registry (CURE) has been designed to improve the scientific understanding, clinical treatment and healthcare planning of CU patients. This report describes the rationale, methods and initial implementation of this registry. METHODS: Chronic Urticaria Registry is an ongoing, prospective, international, multicentre, observational, voluntary registry of patients with CU. Participation in CURE is open to any physician treating CU patients, regardless of location, medical specialty or type of practice setting. CURE aims to collect data on all CU patients, with no intentional selection or exclusion criteria. It collects baseline and follow-up data on the patient's demographics, history, symptoms, trigger and risk factors, therapies and healthcare utilization. RESULTS: Chronic Urticaria Registry is a landmark achievement of the global urticaria medical community. As of 26 February 2020, 39 centres around the world have joined the registry and 35 have entered baseline data on a total of 2946 patients. Publications of this data will be forthcoming soon. CONCLUSIONS: Chronic Urticaria Registry is eagerly seeking the participation of more physicians and the support of more governmental, charitable and commercial sponsors from around the world. Here, in this paper, we invite other physicians to join this unique project to improve the lives of patients with CU.

[Omalizumab for the treatment of chronic urticaria: Real-life findings]. / Traitement de l'urticaire chronique par omalizumab : données en vie réelle.

OBJECTIVE: Assessment of the efficacy and safety of omalizumab in chronic urticaria refractory to conventional treatment (H1-antihistamines at high dosage and montelukast) in real-life practice. PATIENTS AND METHODS: A retrospective, descriptive, single-centre study was performed of the data for all patients presenting refractory chronic spontaneous urticaria or inducible urticaria and receiving omalizumab (300mg every four weeks) from November 2012 to June 2016. RESULTS: In all, 23 patients were included. Omalizumab led to complete or significant remission in 19 patients (83%) with chronic urticaria, with remission in 9 patients (47%) occurring within 72hours of the first injection. One patient had a partial response and 3 (13%) showed no response. Only 2 patients (9%) in complete remission stopped their treatment at 1 and 3 years. 52% of patients presented non-serious adverse events, which in one case resulted in treatment withdrawal. CONCLUSION: Omalizumab exhibited good real-life efficacy in a small series of chronic urticaria patients in France.

The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria.

This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

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.

Chronic urticaria and hormones: Is there a link?

BACKGROUND: While the role of oestrogens in bradykinin angioedema (AE) has been clearly demonstrated, scarce data are available about the role of sex hormones in chronic urticaria (CU). OBJECTIVES: To gather information from a population of women with various forms of CU [chronic spontaneous urticaria (CSU), including a subtype of isolated histaminic AE and a classic subtype of association of wheals and AE, and exclusive inducible urticaria (IU)] about the impact of sex hormones and reproductive factors on their symptoms. METHODS: This was a cross-sectional study comprising interviews of 200 women consulting for CU at nine centres throughout France between May and July 2013. The dermatologists filled in an online questionnaire on the impact of reproductive factors (puberty, contraception and pregnancy) and hormonal treatments on the course of CU, including CSU and IU, in the presence of the women. RESULTS: Most of the women did not experience CU before puberty and if so, puberty did not influence the course of CU. Only 16 women had experienced a pregnancy during CU which caused a worsening of symptoms in four. Hormonal contraception was associated with aggravation in a minority of women, mostly women with CSU (10%). Women with isolated histaminic AE did not exhibit any female sex hormone dependency. CONCLUSIONS: It would appear that sex hormones act as a trigger in only a small subset of women with CU. Nevertheless, this should be taken into account to improve patient management.

The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update.

This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

Methods report on the development of the 2013 revision and update of the EAACI/GA2 LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria.

This methods report describes the process of guideline development in detail. It is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS) and is published in Allergy 2014; 69:868-887.

[Interest of allergy tests in urticaria]. / Place du bilan allergologique dans l'urticaire.

Urticaria is a common skin disease that may affect 20 % of the general population. Most of the time, urticaria is an acute disorder that rarely can be chronic. The difficulty in urticaria is not the clinical diagnosis because the rash is characteristic, but the underlying causes and treatment that result. Urticaria is a benign disease when chronic and potentially dangerous when acute and associated with allergy. This allergy risk, needs an allergy exploration, based on skin tests and / or specific IgE assays. Because allergy is unusual in chronic urticaria, no allergy tests should be performed. By contrast, these tests must be undertaken in case of acute urticaria with a strong suspicion of IgE-mediated reaction because of the risk of severe anaphylaxis in case of allergenic re-exposure.

[Contact urticaria induced by hydrolyzed wheat proteins in cosmetics]. / Urticaire de contact aux hydrolysats de protéines de blé contenus dans des cosmétiques.

BACKGROUND: Hydrolyzed wheat protein, produced by hydrolysis of gluten, is used in certain cosmetics and foods as emulsifiers and stabilizers. It can induce contact urticaria to cosmetics and/or anaphylaxis to food via an immunologic mechanism. PATIENTS AND METHODS: A 28-year-old female beautician presented recurrent contact urticaria, initially on the hands and then more diffused, immediately after applying cosmetics of the same brand containing hydrolyzed wheat protein. Skin tests were positive with the cosmetics and with the hydrolyzed wheat protein contained therein. A 34-year-old woman presented four episodes of generalized urticaria after eating industrially prepared foods. She had also experienced contact urticaria with cosmetics. Skin tests with hydrolyzed wheat protein were positive. For both patients, withdrawal of cosmetics and foods containing hydrolyzed wheat protein led to the regression of symptoms. They were both tolerant to traditional wheat products, such as bread and pastries. DISCUSSION: Although contact urticaria to hydrolyzed wheat protein is rarely described, it must be understood since treatment by eradication of this product is simple and because contact urticaria may precede food allergy. Patients are tolerant to products containing unmodified wheat protein.

[Management of drug reaction with eosinophilia and systemic symptoms (DRESS)]. / Prise en charge du drug reaction with eosinophilia and systemic symptoms (DRESS).

OBJECTIVE: The management of drug-induced hypersensitivity syndrome or drug reaction with eosinophilia and systemic symptoms (DRESS) is not codified. Demonstration of the reactivation of Herpesviruses illustrates the specific pathophysiology of this syndrome. Proposals for the management of DRESS were elaborated by the cutaneous adverse drug reaction working group of the French Society of Dermatology to help with its management. METHODS: From a review of literature and the experience of the members of this group, consensual proposals were written about diagnostic criteria, tests, treatment options, and follow-up. These proposals will need to be validated in prospective studies. RESULTS: A decisional tree of treatment options is proposed, based on the severity of visceral manifestations. The importance of a rapid withdrawal of the culprit drug and of a long-term follow-up is underlined. Treatment will be adapted to the clinicobiological status (topical corticosteroid, systemic corticosteroid, intravenous gammaglobulins, antivirals).

The definition and diagnostic testing of physical and cholinergic urticarias--EAACI/GA2LEN/EDF/UNEV consensus panel recommendations.

The recommendations for the definition and diagnosis presented in this position paper are the result of a panel consensus meeting held in December 2008 in Berlin. This consensus meeting was a joint initiative of EAACI (European Academy of Allergology and Clinical Immunology) Dermatology Section, the EU-funded network of excellence, GA(2)LEN (Global Allergy and Asthma European Network), the EDF (European Dermatology Forum) and UNEV (urticaria network e.V.). The aim of these recommendations is to improve the diagnosis and management of patients with physical urticaria or cholinergic urticaria and to promote research and a better understanding of these diseases. Our recommendations used the paper produced by a 1996 expert meeting (1) and they acknowledge the latest changes in our understanding of physical urticarias and cholinergic urticaria as well as the recent development of novel diagnostic tools. In addition, this consensus paper highlights areas of need for further research.

[Cheilitis: a new manifestation of gastro-oesophageal reflux?]. / Chéilite sèche : nouvelle manifestation du reflux gastro-oesophagien ?

BACKGROUND: Gastro-oesophageal reflux (GOR) is a common disease. Extra-oesophageal clinical signs associated with the disease and affecting the ENT (otitis media, rhinitis, laryngitis), pulmonary and stomatological spheres have been described for a number of years. We report three cases of cheilitis potentially attributable to GOR. CASE REPORT: Three female patients consulted for cheilitis present for several months. Screening for an infectious cause was negative, as was allergological investigation using skin tests. However, questioning revealed nocturnal breathing through the mouth in all three patients as well as symptomatic GOR in one patient. Test therapy comprising proton-pump inhibitors was proposed and after 1month symptoms had subsided completely. Gastro-oesophageal endoscopy performed in the subsequent weeks revealed oesophagitis in all patients. DISCUSSION: Extra-oesophageal signs described during the course of GOR mainly affect the ENT sphere and pulmonary sphere (cough, asthma) and are doubtless due to the direct caustic action of gastric secretions on the mucus membrane. Although gastroenterological investigation (endoscopy, 24-h pHmetry) may be negative, treatment with proton-pump inhibitors results in complete resolution of symptoms. The cases we describe suggest for the first time that extra-oesophageal sites affected by GOR may include the labial semimucosa.

[Safety of reintroducing platelet-inhibitory doses of aspirin in patients with urticaria or angioedema induced by anti-inflammatory doses]. / Réintroduction de l'aspirine à dose antiagrégante après urticaire ou angio-oedème induits par des doses anti-inflammatoires.

BACKGROUND: Aspirin is one of the most widely prescribed drugs in the world on account of its analgesic, antipyretic, and anti-inflammatory properties. Its effect on platelet aggregation makes it the first choice for prophylaxis in cardiovascular, neurological and obstetric diseases. However, a history of aspirin-induced urticaria and/or angioedema is usually a contraindication for further prescription of the drug. The aim of this article was to demonstrate that patients presenting aspirin-induced cutaneous reactions at anti-inflammatory doses can safely benefit from aspirin reintroduction at platelet-inhibitory doses. PATIENTS AND METHODS: Patients with a history of aspirin-induced urticaria and/or angioedema referred to our department between January 2000 and June 2008 for double-blind placebo-controlled reintroduction at platelet-inhibitory doses for a medical indication were enrolled in this study. RESULTS: Seventy patients with aspirin hypersensitivity as well as a medical indication for this therapy were referred to our department. Of these, 38 (54.3%) had a history of aspirin-induced urticaria and/or angioedema, including three laryngeal oedemas (7.9%). All subjects received platelet-inhibitory doses of aspirin (maximal total dose: 400mg/day) in double-blind placebo-controlled fashion during a one-day hospitalization period. None of the patients presented an immediate hypersensitivity reaction. Only one patient, who had received a cumulative dose of 200mg/day, reported diffuse urticaria and facial angioedema of no clinical significance the following day. He had a history of chronic urticaria. CONCLUSION: This article demonstrates the safety of reintroducing platelet-inhibitory doses of aspirin in patients in whom it is indicated and reporting aspirin-induced urticaria and/or angioedema with anti-inflammatory doses. However, patients with a history of chronic urticaria should undergo a challenge with the lowest platelet-inhibitory dose (75mg/day) in order to minimize the risk of aggravating their condition.

Physician and patient survey of allergic rhinitis in France: perceptions on prevalence, severity of symptoms, care management and specific immunotherapy.

BACKGROUND: Specific immunotherapy (SIT) is the only aetiological treatment used in allergic rhinitis (AR). A telephone survey of patients and physicians in France was carried out to understand better the real and perceived advantages and inconveniences of this therapeutic approach. METHODS: A cohort of 453 individuals with AR was selected using the Score For Allergic Rhinitis questionnaire. The survey evaluated the level of understanding of allergic rhinitis and its management, including both pharmacotherapy and SIT. A parallel survey was conducted with 400 general practitioners, allergists and nonallergist specialists. RESULTS: Approximately 50% of patients had heard about SIT as a therapeutic option. Of these, 56% had a positive view of SIT and 14% a negative image. A majority of patients and physicians with a positive opinion associated SIT with improved well-being and quality of life, while those with a negative opinion considered it to be a long and inconvenient treatment, with uncertain results. Over 50% of patients who had been offered SIT had accepted it and approximately 60% of these were satisfied with it. The future availability of SIT as sublingual tablets was perceived positively by both patients and physicians. CONCLUSIONS: Many patients with AR are unaware of their pathology and few seek help from health professionals. When patients take medication, they are generally satisfied with their treatment, even if it is only symptomatic. Patients and physicians see the notion of definitive recovery as the main benefit of SIT, whereas the main disadvantage is the duration of treatment.

[Intolerance to sulfonamides in HIV infected subjects. Toxic and allergic origin]. / Intolérance aux sulfamides chez les sujets infectés par le VIH. Origine toxique et allergique.

Intolerance to sulfonamides is very frequent in HIV-infected subjects and 10 times more common than in the general population. There are 2 types of intolerance to sulfonamides: early reactions with urticaria or angioedema, which are IgE-dependent, and late reactions with febrile rash, which occur between the 6th and 12th days of treatment and represent the vast majority of allergic manifestations in HIV-infected subjects. Clinically, these reactions resemble serum sickness, but all physiopathological hypotheses point to toxic process. The degradation of sulfonamides has two different pathways: the N-acetylation pathway which is genetically determined and saturable, and the cytochrome P450 pathway which produces toxic hydroxylamine metabolites "detoxified" by glutathione. In HIV-infected subjects detoxication is thought to be incomplete due to an acquired deficiency of glutathione and probably increased in the presence of a slow acetylation profile.

[Cutaneous reactions to heparin: immunological and clinical aspects]. / Réactions cutanées à l'héparine: aspects immunologiques et cliniques.

Skin reactions to heparin are rare, the most frequent manifestation being skin necrosis. Reactions occur either as an isolated manifestation or within a context of heparin-induced thrombopenia. Urticarious and eczematous reaction, either localized at injection sites or with a general distribution, have been recently reported. In all cases, it is mandatory to withdraw heparin therapy. Such accidents can be observed with all types of heparin (standard heparin and low-molecular weight heparin). Cross-reactions between two types of heparin are frequent. Skin tests can be used to guide heparintherapy.

[Drug-induced chronic urticarias]. / Urticaires chroniques d'origine médicamenteuse.

Urticaria is a classic cutaneous manifestation of drug allergy considered like the second most frequent drug eruption after maculopapular exanthemas. Most of the time drugs are responsible of acute urticaria lasting less than 24 hours. The mechanisms of these acute urticarial reactions are multiple, mostly related to an IgE-induced reaction. Nevertheless, some drugs can induce immune complexes and activate the complement cascade (sickness disease). Others may directly release mast cells mediators or activate complement by non immunologic mechanisms in the absence of antibody. In every case, these drugs are unable to generate urticaria during more than 6 weeks, time allowed for calling a chronic urticaria. However drugs like nonsteroidal anti-inflammatory drugs and acetysalicylic acid can, by a pharmacologic mechanism, exacerbate or trigger chronic urticaria. Angiotensin-converting enzyme inhibitors, by a defect of degradation of bradykinin, may also induced angioedemas. In this context, if an allergologic investigation is useful in the exploration of acute urticaria, it seems useless for chronic urticaria.

[Vibratory angioedema]. / Angio-oedème vibratoire.

BACKGROUND: Vibratory angioedema is a rare form of physical urticaria. This entity can be an hereditary autosomal dominant disorder or an acquired sporadic disease. Immediate and delayed forms have been reported. CASE-REPORT: A 34-year-old woman was referred to us for a vibratory angioedema induced by mountain biking. Despite her handicap, she could provoke a clinical tolerance with disappearance of pruritus but not of erythema and edema if she continued her physical effort. Diagnosis was confirmed with a vibratory stimulus using a Vortex for 5 minutes. The realization of a controlled vibratory stimuli among 20 volunteers induced a positive response in 7 cases (35 p. 100). DISCUSSION: These results raise the problem of the specificity of the test but also point out the possible physiological response of the body to intense vibratory stimulations.