Cross-cultural adaptation and validation of the RhinAsthma Patient Perspective (RAPP) in Spanish.

OBJECTIVE: the RhinAsthma Patient Perspective (RAPP) is the only available tool to assess HRQoL in daily practice. The aim of this study is to cross-culturally validate the RAPP in Spanish. METHODS: The RAPP was translated into Spanish. Adult patients receiving usual care for asthma and allergic rhinitis (AR) were recruited consecutively and assessed twice with a four-week interval between visits to test the psychometric properties of the questionnaire. RESULTS: 149 patients (62.8% female) with a mean age of 37.7 years completed the study. Exploratory and confirmatory factor analysis confirmed the uni-dimensional structure of the questionnaire. Internal consistency (0.73 at visit 1; 0.87 at visit 2), convergent and discriminant validity (p<.05 at both visits) were satisfactory. Reliability was confirmed by an ICC of 0.69 and a CCC of 0.74. Responsiveness was supported by a significant association with VAS (r=0.28, p<0.003) and ACT (r=-0.35, p<0.01). The minimal clinical difference (MID) value in the analyzed population was 2. CONCLUSIONS: The Spanish version of RAPP was demonstrated to have satisfactory psychometric properties and is a valid, reliable and responsive tool for the assessment of asthma and AR HRQoL in clinical practice.

The international WAO/EAACI guideline for the management of hereditary angioedema-The 2017 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: (1) How should HAE-1/2 be defined and classified?, (2) How should HAE-1/2 be diagnosed?, (3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, (4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and (5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures?

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.

Scabies, crusted (Norwegian) scabies and the diagnosis of mite sensitisation.

Scabies is observed with relatively high frequency in Allergy and Dermatology clinics in developing countries where poor sanitary conditions are prevalent and increasingly in some areas of the world with increased immigrant populations. Since the immunological response to scabies mites includes the production of IgE class antibodies to Sarcoptes scabiei allergens which cross-react with Dermatophagoides major allergens Der p 1 and Der p 2, positive immediate-type skin tests to house dust mite extracts should be interpreted cautiously. Additionally, scabies should be included routinely in the differential diagnosis of itchy rashes in patients living in those areas.

Biomarkers of treatment efficacy in patients with chronic spontaneous urticaria.

Summary: Background. Currently there are no biomarkers useful to predict the future evolution and the therapeutic response in patients with chronic spontaneous urticaria (CSU). Objective. To review the available information on biomarkers that might be applied for the follow up of the response to guideline recommended therapies for CSU. Methods. A review of the medical literature on CSU potential clinical and laboratory biomarkers in PubMed and MEDLINE including the terms urticaria, chronic urticaria, chronic idiopathic urticaria, chronic spontaneous urticaria, antihistamines (AHs), omalizumab (OMA), cyclosporine (CyA), and treatment. Results. Clinical manifestations that were associated to poor responses to AHs were atopy, asthma, rhinitis / rhinosinusitis, thyroid disease, hypertension, higher disease activity and duration. Laboratory markers of AH resistance that have been reported include Complement C5a fraction, Autologous Serum Skin Test (ASST), Basophil Activation Test (BAT), D-dimer and LCN2 adipokine. Basophil Histamine Release Assay (BHRA), ASST, and basophil CD203c-upregulating activity in the serum correlated with favorable response to OMA, whereas disease duration and severity, BAT, BHRA, and D-dimer levels were associated with better responses to CyA. Conclusion. Some promising biomarkers useful for patient management in CSU, have been identified in the literature. There is, however, an urgent need of new, easy-to-perform markers that can be made widely available for the optimal care of patients suffering CSU.

Factors linked to disease severity and time to remission in patients with chronic spontaneous urticaria.

Biomarkers useful for the evaluation and management of patients with chronic spontaneous urticaria (CSU) are not currently available. A review of various clinical and laboratory markers that have been studied to assess their value for determining the severity or predicting the evolution of disease in adult patients with CSU was carried out. A search of the medical literature on PubMed and MEDLINE including the terms urticaria, chronic urticaria, chronic idiopathic urticaria, CSU, severity, prognosis and treatment was performed. Based on our review of the literature, among the clinical markers studied, higher age at onset, being female, long disease duration and aspirin/NSAID hypersensitivity may be linked to both severe CSU and a long time to spontaneous remission. In addition, a positive autologous serum skin test (ASST) may be associated with severe CSU, and comorbidity of inducible urticaria and concomitant recurrent angio-oedema may be linked to longer CSU duration. Potential biomarkers of CSU severity and/or duration include basophil numbers and susceptibility to activation, inflammatory markers, markers of activation of the extrinsic coagulation pathway, immunoglobulin E and vitamin D. Although the described markers are promising, further studies on representative and well-characterized patient populations are needed to determine the value of these clinical and biological markers for predicting the severity and course of disease in patients with CSU.

Cofactors and comorbidities in patients with aspirin/NSAID hypersensitivity.

Hypersensitivity reactions to aspirin and other NSAIDs occur in individuals genetically predisposed and exhibit different clinical manifestations, especially respiratory, cutaneous, and generalised. Five different phenotypes define distinct clinical pictures: aspirin-exacerbated respiratory disease, aspirin/NSAID cutaneous disease, NSAID-induced urticaria, angio-oedema and anaphylaxis, single NSAID reactions, and delayed reactions. They are observed more frequently in middle-aged women, and in atopic individuals. While ASA/NSAID hypersensitivity shares comorbidities with asthma, chronic rhinosinusitis, nasal polyposis, chronic urticaria and angio-oedema, ASA and other NSAIDs can also be cofactors for other clinically relevant conditions, especially food-dependent exercise-induced anaphylaxis, angio-oedema induced by angiotensin-converting enzyme inhibitors, and oral mite anaphylaxis. Awareness on these relationships is required for the correct diagnosis, classification, and treatment of affected patients.

Justification for IgE as a therapeutic target in chronic spontaneous urticaria.

SUMMARY: Monoclonal anti-IgE antibodies (omalizumab) are able to induce clinically significant benefits in patients with severe chronic spontaneous urticaria (CS). Those results led clinicians and investigators to reconsider a possible pathogenic role not previously supported for IgE and its receptors in this disease, and to investigate additional approaches for understanding its pathogenesis. IgE antibodies to unknown environmental allergens able to trigger chronic urticaria are not generally regarded as the etiologic factor for the disease. Other proposed mechanisms for the production of wheals and angioedema in CSU include IgG autoantibodies and CD4-positive T cells directed to the high-affinity IgE receptor, autoantibodies to IgE itself, IgE autoantibodies directed to thyroid and nuclear autoantigens, highly cytokinergic IgE, and histamine-releasing factors able to bind to IgE and cause mast cell activation. It is expected that a better knowledge on the mechanisms leading to CSU and the clarification of the immunological effects of anti-IgE will provide novel therapies for this frequent condition.

Constructing a classification of hypersensitivity/allergic diseases for ICD-11 by crowdsourcing the allergist community.

The global allergy community strongly believes that the 11th revision of the International Classification of Diseases (ICD-11) offers a unique opportunity to improve the classification and coding of hypersensitivity/allergic diseases via inclusion of a specific chapter dedicated to this disease area to facilitate epidemiological studies, as well as to evaluate the true size of the allergy epidemic. In this context, an international collaboration has decided to revise the classification of hypersensitivity/allergic diseases and to validate it for ICD-11 by crowdsourcing the allergist community. After careful comparison between ICD-10 and 11 beta phase linearization codes, we identified gaps and trade-offs allowing us to construct a classification proposal, which was sent to the European Academy of Allergy and Clinical Immunology (EAACI) sections, interest groups, executive committee as well as the World Allergy Organization (WAO), and American Academy of Allergy Asthma and Immunology (AAAAI) leaderships. The crowdsourcing process produced comments from 50 of 171 members contacted by e-mail. The classification proposal has also been discussed at face-to-face meetings with experts of EAACI sections and interest groups and presented in a number of business meetings during the 2014 EAACI annual congress in Copenhagen. As a result, a high-level complex structure of classification for hypersensitivity/allergic diseases has been constructed. The model proposed has been presented to the WHO groups in charge of the ICD revision. The international collaboration of allergy experts appreciates bilateral discussion and aims to get endorsement of their proposals for the final ICD-11.

Treatment dilemmas in chronic urticaria.

The European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA(2) LEN)/European Dermatology Forum (EDF)/World Allergy Organization (WAO) recently published updated recommendations for the classification, diagnosis and management of chronic urticaria (CU). This article discusses several case histories that provide examples of how these recommendations can be implemented in the treatment of CU in a variety of real-life patients.

Management and treatment of chronic urticaria (CU).

Developments increasing our understanding of chronic urticaria have resulted in the simplification and improvement of available treatments. Currently, many treatments target mast cell mediators, but we can now disrupt mast cell activation with the anti-IgE antibody omalizumab, which has markedly advanced the treatment landscape for patients with difficult-to-treat urticaria. Current guidelines provide a framework for the management and treatment of patients with CU but, as each patient is different, knowledge and experience of specialist dermatologists and allergists are key to effective pharmacotherapy. This article reviews the different therapeutic options for patients with chronic spontaneous urticaria (also called chronic idiopathic urticaria) or chronic inducible urticaria and discusses management of special populations or special circumstances related to CU.

Aspirin-exacerbated cutaneous disease (AECD) is a distinct subphenotype of chronic spontaneous urticaria.

BACKGROUND: A subset of patients with chronic spontaneous urticaria (CSU) experience disease exacerbations after receiving non-steroidal anti-inflammatory drugs (NSAIDs). This condition has been designated as Aspirin-Exacerbated Cutaneous Disease (AECD). OBJECTIVES: The purpose of this study was twofold: (i) Investigate the demographic and clinical features of patients affected by AECD; (ii) To compare patients with AECD and NSAID-tolerant CSU patients for those characteristics. METHODS: Patients with AECD and a group of unselected CSU patients tolerant to NSAIDs were studied. Demographic and clinical data were obtained by direct questioning and physical examination. Laboratory investigations and allergen skin prick tests were performed only in selected patients, as guided by the medical history. RESULTS: Of 423 CSU patients admitted in the clinics, 52 (12.2%) had AECD. Compared with NSAID-tolerant CSU patients, AECD patients had significantly longer disease duration (57.7 ± 118.4 vs. 24.4 ± 36.6 months, P < 0.05), higher prevalence of angio-oedema (72.7 vs. 30.9%, P < 0.05) and atopy (83.8% vs. 58.4%, P < 0.05) and more frequent involvement of the face and upper respiratory tract (54.5% vs. 29.6%, P < 0.05). CONCLUSIONS: AECD is a distinct phenotype that should be considered for inclusion as a separate subtype of chronic spontaneous urticaria.

Demographic and clinical profiles in patients with acute urticaria.

BACKGROUND: Urticaria is a common cause for consultation in general and specialised medical practices. There is scarce information on the characteristics of patients suffering acute urticaria in Latin America. OBJECTIVES: To investigate demographic and clinical features of patients with acute urticaria attending two allergy clinics in Caracas, Venezuela. METHODS: A prospective study of all new patients who consulted during a three-year period because of acute urticaria. Information on age, gender, symptom duration, previous medical history, body distribution of wheals and angio-oedema, laboratory investigations, skin prick tests, and pharmacological treatment, was collected. Patients were classified according to their age as children/adolescents and adults. RESULTS: Two hundred and forty eight patients (177 adults and 71 children) were studied. Acute urticaria was more frequent in middle-aged atopic female patients. Lesions more often involved upper and lower limbs and head, and 31% of patients exhibited generalised urticaria. Laboratory investigations, performed only in selected cases, did not contribute to the final diagnosis. Most frequent subtypes of acute urticaria were spontaneous, dermographic, papular, and drug-induced urticaria. Most patients were treated with non-sedating antihistamines, with increased use of cetirizine and levocetirizine in children, while 5.6% of children and 20.3% of adults required the addition of short courses of systemic corticosteroids. CONCLUSIONS: Acute urticaria is a frequent cause of consultation for allergists, affecting more often middle-aged female atopic patients. The use of extensive complementary tests does not seem to be cost-effective for this clinical condition. Spontaneous, dermographic, papular and drug-induced urticaria are the most common subtypes.

Global classification and coding of hypersensitivity diseases - An EAACI - WAO survey, strategic paper and review.

Hypersensitivity diseases are not adequately coded in the International Coding of Diseases (ICD)-10 resulting in misclassification, leading to low visibility of these conditions and general accuracy of official statistics. To call attention to the inadequacy of the ICD-10 in relation to allergic and hypersensitivity diseases and to contribute to improvements to be made in the forthcoming revision of ICD, a web-based global survey of healthcare professionals' attitudes toward allergic disorders classification was proposed to the members of European Academy of Allergy and Clinical Immunology (EAACI) (individuals) and World Allergy Organization (WAO) (representative responding on behalf of the national society), launched via internet and circulated for 6 week. As a result, we had 612 members of 144 countries from all six World Health Organization (WHO) global regions who answered the survey. ICD-10 is the most used classification worldwide, but it was not considered appropriate in clinical practice by the majority of participants. The majority indicated the EAACI-WAO classification as being easier and more accurate in the daily practice. They saw the need for a diagnostic system useful for nonallergists and endorsed the possibility of a global, cross-culturally applicable classification system of allergic disorders. This first and most broadly international survey ever conducted of health professionals' attitudes toward allergic disorders classification supports the need to update the current classifications of allergic diseases and can be useful to the WHO in improving the clinical utility of the classification and its global acceptability for the revised ICD-11.

International Consensus on drug allergy.

When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term 'allergy') are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.

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.

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).

Mite hypersensitivity in patients with rhinitis and rhinosinusitis living in a tropical environment.

PURPOSE: Rhinitis and rhinosinusitis are major concerns in public health. Mites are important aetiological agents in the tropics. The present study investigated the in vivo response to mite allergens in patients with rhinitis and rhinosinusitis. METHODS: All patients with presumptive nasal allergy were included. Skin tests were done with inhalants and mite extracts. Patients were classified as allergic or non-allergic according to skin tests and history. RESULTS: Out of 229 patients, 175 (76.4%) showed positive skin tests. Allergic patients showed positivity to mites in 97.1% of cases, 51.4% to dog dander; 40.5% to cat dander; 36.5% to German cockroach; 22.8% to moulds; and 21.1% to grass pollens. Dermatophagoides farinae induced responses in 90.8% of patients, D. pteronyssinus in 90.1%, Blomia tropicalis in 74.8%, Glycyphagus domesticus in 62.2%, Chortoglyphus arcuatus in 58.2%, Acarus siro in 46.2%, Lepidoglyphus destructor in 35.4%, and Tyrophagus putrescentiae in 35.0%. Higher correlations were found between skin test diameters induced by mites from the same family. CONCLUSIONS: Sensitisation to inhalant allergens is present in 76% of allergy clinics' patients with rhinitis or rhinosinusitis. Our results confirm previous observations showing that mites constitute the most important cause of respiratory allergy in tropical settings and suggest that mite allergen cross-reactivity is responsible for the positivity of skin tests to mites not present in the patient's environment since the species Glycyphagus, Chortoglyphus, Acarus, Lepidoglyphus and Tyrophagus have not been found in Caracas house dust.

Subtypes of chronic urticaria in patients attending allergy clinics in Venezuela.

Chronic urticaria (CU) is one of the most puzzling clinical entities confronted by the medical profession. It is a common motive for consultation, and in a sizable proportion of patients no identifiable cause is evident. Since there are relatively few publications regarding CU in developing countries, we performed a prospective 3-year study on the demographic and clinical features of patients with CU. Four hundred and twenty-three subjects were studied, 52 children and 371 adults, 295 females (69.7%), with a mean age of 38.4 ± 17.8 years. More often, wheals and angioedema (AE) were present on the head, upper and lower limbs and the trunk. AE was present in 162 patients (38.4%). The most frequent subtypes were chronic spontaneous urticaria, aspirin-exacerbated cutaneous disease, dermographic urticaria, and combinations of various subtypes. A better understanding of the characteristics of patients suffering CU is helpful for clinicians dealing with this ailment, and provides guidance for new investigations on its pathogenesis, which will hopefully result in a better management of this vexing condition.