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The European Academy of Dermatology and Venereology (EADV) Task Forces on quality of life (QoL) and patient‐oriented outcomes and on urticaria and angioedema recommendations for the assessment of Health‐related (HR) QoL in all patients with urticaria in research and practice are as follows: to use the DLQI for adults and the CDLQI for children as dermatology‐specific and the CU‐Q2oL as a disease‐specific HRQoL instruments in urticaria; to use generic instruments to provide comparison of data on urticaria with non‐dermatologic diseases, or to compare with healthy volunteers or the general population; to select validated HRQoL instruments with appropriate age limits; to present exact numeric data for HRQoL results; correct title of any HRQoL instrument should be used, along with its correct abbreviation and the reference to its original publication, where possible. The EADV TFs discourage the use of non‐validated HRQoL instruments and modified HRQoL instruments that have not undergone standard validation. [ABSTRACT FROM AUTHOR]

Phenoxyethanol, or 2‐phenoxyethanol, has a large spectrum of antimicrobial activity and has been widely used as a preservative in cosmetic products for decades. It is effective against various Gram‐negative and Gram‐positive bacteria, as well as against yeasts, and has only a weak inhibitory effect on resident skin flora. According to the European Scientific Committee on Consumer Safety, phenoxyethanol is safe for all consumers – including children of all ages – when used as a preservative in cosmetic products at a maximum concentration of 1%. Adverse systemic effects have been observed in toxicological studies on animals but only when the levels of exposure were many magnitudes higher (around 200‐fold higher) than those to which consumers are exposed when using phenoxyethanol‐containing cosmetic products. Despite its widespread use in cosmetic products, phenoxyethanol is a rare sensitizer. It can be considered as one of the most well‐tolerated preservatives used in cosmetic products. [ABSTRACT FROM AUTHOR]

Octocrylene or octocrilene is an organic ultraviolet (UV) filter which absorbs mainly UVB radiation and short UVA wavelengths. It is used in various cosmetic products to either provide an appropriate sun protection factor in sunscreen products or to protect cosmetic formulations from UV radiation. There is no discussion that UV filters are beneficial ingredients in cosmetics since they protect from skin cancer, but octocrylene has been recently incriminated to potentially induce adverse effects on the endocrine system in addition to having allergic and/or photoallergic potential. However, the substance has the advantage to work synergistically with other filters allowing a beneficial broad photoprotection, e.g. it stabilizes the UVA filter avobenzone (i.e. butylmethoxydibenzoylmethane). Like all chemicals used in cosmetics, the safety profile of octocrylene is constantly under assessment by the European Chemical Agency (ECHA) since it has been registered according to the European regulation Registration, Evaluation, Authorisation and Restriction of Chemicals. Summaries of safety data of octocrylene are publicly available on the ECHA website. This review aims to present the main safety data from the ECHA website, as well as those reported in scientific articles from peer‐reviewed journals. The available data show that octocrylene does not have any endocrine disruption potential. It is a rare sensitizer, photocontact allergy is more frequent and it is considered consecutive to photosensitization to ketoprofen. Based on these results, octocrylene can be considered as safe when used as a UV filter in cosmetic products at a concentration up to 10%. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Summary: Background: Cholinergic urticaria (CholU), a common form of chronic inducible urticaria, is characterized by itchy weals that occur in response to physical exercise or passive warming. CholU patients frequently exhibit a high burden of disease. As of yet, no specific instrument is available to assess their disease‐related quality‐of‐life (QoL) impairment. Objective: The aim of this study was to develop and validate the first disease‐specific QoL instrument for CholU patients, the Cholinergic Urticaria Quality‐of‐Life Questionnaire (CholU‐QoL). Methods: Using a combined approach of the literature search, semistructured patient interviews and expert opinion, we developed 96 potential CholU‐QoL items. Subsequent item selection was performed by means of impact analysis complemented by an expert review for face validity. The resulting final CholU‐QoL was then tested for levels of validity, reliability and influence factors in 88 CholU patients. In parallel, an US American‐Canadian English version of the CholU‐QoL was developed. Results: The final 28‐item CholU‐QoL was found to have a 5‐domain structure (“symptoms,” “functional life,” “social interaction,” “therapy,” “emotions”) with excellent internal consistency. The CholU‐QoL also showed a valid total score, and good levels of convergent validity, known‐groups validity, as well as test‐retest reliability. Multiple regression analysis found no significant drivers of the CholU‐QoL total score. Conclusions and Clinical Relevance: The CholU‐QoL is the first disease‐specific QoL instrument for CholU and also the first specific QoL measure in the field of chronic inducible urticarias. It may serve as a valuable tool for clinical trials and improve routine patient management. [ABSTRACT FROM AUTHOR]

Background: Quantification of burden of chronic spontaneous urticaria (CSU) vs. psoriasis (PsO) is limited. Objective: To evaluate the burden associated with CSU vs. PsO of all severities (overall PsO), mild and moderate/severe PsO. Methods: This retrospective cross-sectional analysis compared data from adult patients with chronic urticaria (CU), used as a proxy for CSU, and PsO from the National Health and Wellness Survey in France, Germany, Italy, Spain and the United Kingdom. Outcomes included mental and physical component summary scores (MCS and PCS) calculated from the Short Form (SF)-36v2 or SF-12v2, SF-6D health utility scores, self-reported psychological complaints (anxiety, depression and sleep difficulties), work productivity and activity impairment, and self-reported healthcare resource utilization. Bivariate and multivariate analyses for each outcome and comparative groups were conducted. Results: This analysis included 769 CU and 7857 PsO (26.9% moderate/severe) patients. Following adjustment for covariates, CU patients showed a greater health-related quality of life (HRQoL) impairment vs. overall PsO (MCS: -2.4, PCS: -1.6, SF-6D: -0.03; all P < 0.001). CU patients showed a higher risk of anxiety, depression and sleep difficulties [odds ratio (OR): 1.63, 1.34 and 1.56, respectively; all P < 0.01] and greater healthcare resource use vs. overall PsO. The overall activity impairment was significantly greater in CU patients than in overall PsO patients (P = 0.001), while the impact on work was not significantly different. The results vs. moderate/severe PsO group showed no significant differences on all outcomes. Conclusion: Burden of illness in CU is higher than PsO of all severities but similar to that observed in moderate/severe PsO. Both diseases have a similar negative impact on work productivity. [ABSTRACT FROM AUTHOR]

While allergic mast cell ( MC) degranulation occurs by Fcε RI aggregation and varies in strength among subjects, the analogous pseudo-allergic route was recently uncovered to proceed via MRGPRX2. Here, we examine interindividual variability in skin MC responses to Fcε RI triggering vs those evoked by MRGPRX2. While population-based variability is comparable between the routes, Fcε RI- and MRGPRX2-stimulated pathways are completely independent from each other, and responsiveness to one has therefore no predictive value for the other. Conversely, degranulation triggered by compound 48/80 is highly correlated to the process elicited by substance P. MRGPRX2 mRNA shows pronounced population-based variability (coefficient of variation 102.9%). Surprisingly, stem cell factor ( SCF) as the MC-supportive mediator par excellence potently inhibits pseudo-allergic degranulation, while it simultaneously promotes allergic stimulation via Fcε RI . We conclude that SCF can have selective MC-dampening functions. Clinically, the data imply that subjects highly reactive in one pathway are not automatically hyper-responsive in terms of the alternative route. [ABSTRACT FROM AUTHOR]

The Future of the Allergists and Specific Immunotherapy ( FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy ( AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardization of practice in the treatment of allergies. This review presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future. [ABSTRACT FROM AUTHOR]

Precision medicine ( PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis ( AR) and chronic rhinosinusitis ( CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second-level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment. [ABSTRACT FROM AUTHOR]

Background Topical corticosteroids may be needed for treating skin conditions in pregnancy. Nevertheless, only limited data on the fetal effects of topical corticosteroids are available. Objective To update an evidence-based guideline on the safe use of topical corticosteroids in pregnancy. Methods A guideline subcommittee of the European Dermatology Forum updated the guideline by adding and appraising new evidence. Results The current best evidence from 14 observational studies with 1 601 515 study subjects found no significant associations between maternal use of topical corticosteroids of any potency and some adverse pregnancy outcomes including mode of delivery, birth defect, preterm delivery and fetal death. However, maternal use of potent/very potent topical corticosteroids, especially in large amounts, is associated with an increase in the risk of low birthweight. Conclusion Mild/moderate topical corticosteroids should be preferred to potent/very potent ones in pregnancy. The well-known topical side-effects of corticosteroids on the mother's side need to be considered as well. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis ( AD) is a common skin disorder. Its diagnosis relies on clinical judgment. Mild and untypical manifestations may cause diagnostic difficulties. Biomarkers for the differential diagnostic workup of AD are needed. Objective To test whether the results of skin provocation with cowhage, an established model of histamine-independent pruritus, and histamine are different in AD patients and healthy subjects and whether these tests may be used as diagnostic markers of AD. Methods Twenty-two AD patients and 18 healthy controls were subjected to topical cowhage provocation and skin prick testing with histamine and assessed for differences in the quality, intensity, and persistence of itch, for wheal diameter, volume, and flare size and intensity. Results Patients with AD, compared with healthy controls, exhibited significantly smaller histamine-induced flares ( P < 0.01) and markedly longer itch persistence after provocation with cowhage ( P < 0.01). Both parameters showed good diagnostic properties for AD (area under the receiver operating characteristic ( ROC) curve 0.78 and 0.80, respectively). The persistence of cowhage-induced itch for at least 30 min and a histamine-induced flare of less than 2 cm in diameter were reliable thresholds for the diagnosis of AD. If combinations of the results of both tests were used, their sensitivity and specificity of diagnosing AD were up to 91% and 94%, respectively. Conclusion The clinical benefit of cowhage and histamine skin provocation tests should be investigated in further studies. Long persistence of cowhage-induced itch and diminished histamine-induced flare in nonlesional skin may support diagnosis of AD. [ABSTRACT FROM AUTHOR]

Me DALL (Mechanisms of the Development of ALLergy; EU FP7- CP- IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. Me DALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: Me DALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, Me DALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. Me DALL has deployed translational activities within the EU agenda. [ABSTRACT FROM AUTHOR]

Background Histamine intolerance and pseudoallergy to foods have been suggested to be causes of chronic spontaneous urticaria ( CSU) with some patients reporting exacerbation with histamine-rich foods. Objective The study aim was to identify the rate of histamine-intolerant CSU patients and to characterize the relevance of histamine intolerance as an underlying cause of CSU. Methods A cohort of 157 of moderate to severe CSU patients ( UAS7 ≥ 10) was asked to provide a detailed clinical history, particularly in relation to symptom development after eating histamine-rich foods. They subsequently undertook a histamine-free pseudoallergen-low diet followed by a double-blind, placebo-controlled oral histamine provocation (75 mg). Results One third of patients (34%) had a positive history of histamine intolerance. There was no statistical difference between the mean UAS7 scores of patients with positive and negative histories (22.4 ± 1.0 vs. 22.7 ± 0.8). When kept on diet, 46% of patients responded with reduced CSU activity ( UAS7 reduction of ≥7). Following double-blind, placebo-controlled oral histamine provocation, 17% of patients gave a positive weal response. There appeared to be little relationship between patient history, response to diet and the weal response to oral histamine provocation. First, the history-positive and -negative groups contained similar proportions of diet and histamine provocation weal-positive patients. Second, the diet-positive and -negative groups contained similar proportions of history-positive and histamine provocation weal-positive patients. Third, the histamine provocation weal-positive and -negative groups had similar rates of history- and diet-positive patients. Finally, only 2 of the 157 patients were positive in all three domains. Conclusions CSU due to histamine intolerance appears to be rare and cannot be diagnosed based on the history. The study confirms that avoidance diets low in pseudoallergens can improve urticaria symptoms, this is probably not due to the absence of dietary histamine. [ABSTRACT FROM AUTHOR]

Background GA² LEN, 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 GA² LEN UCAREs. Results The main aims of GA² LEN 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 GA² LEN 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 GA² LEN UCARE program will result in a strong network of urticaria specialists, promote urticaria research, and harmonize and improve urticaria management globally. [ABSTRACT FROM AUTHOR]

Abstract: This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. Despite the clear international guideline, there remain a number of controversies and challenges in the management of patients with chronic urticaria (CU). As a result of major advancements in urticaria over the past 4 years, the current EAACI/GA2LEN/EDF/WAO urticaria guideline treatment algorithm requires updating. Case studies from patients with chronic spontaneous urticaria (CSU) [also called chronic idiopathic urticaria (CIU)], chronic inducible urticaria (CIndU) or diseases and syndromes related to CU are useful in describing and exploring challenges in disease management. Case studies of specific CSU patient populations such as children with CU or patients with angio‐edema but no hives also require consideration as potentially challenging groups with unmet needs. The current EAACI/GA2LEN/EDF/WAO urticaria guideline provides a general framework for the management of patients with CU but, as these cases highlight, a personalized approach based on the expert knowledge of the physician may be required. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The European Academy of Allergy and Clinical Immunology ( EAACI), the European Rhinologic Society ( ERS), and the European Medical Association ( EMA) organized, on October 14, 2015, a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP David Borrelli, and with active participation of the EU Commissioner for Health and Food Safety Vytenis Andriukaitis, MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, the European Respiratory Society ( ERS), the European Federations of Allergy and Airways Diseases Patients Associations ( EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma ( ARIA), and the Respiratory Effectiveness Group ( REG). The socioeconomic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic noncommunicable diseases in the EU; 30% of the total European population is suffering from allergies and asthma, and more than half are deprived from adequate diagnosis and treatment. Precision medicine represents a novel approach, embracing four key features: personalized care based on molecular, immunologic, and functional endotyping of the disease, with participation of the patient in the decision-making process of therapeutic actions, and considering predictive and preventive aspects of the treatment. Implementation of precision medicine into clinical practice may help to achieve the arrest of the epidemic of allergies and chronic airways diseases. Participants underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient empowerment, and cost-effective treatment strategies. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 71-year old woman with systemic mastocytosis with history of smoking. It is noted that she was further diagnosed with tripe palms that are characterized clinically by thickened velvety palms with pronounced dermatoglyphics. The article mentions that Anaplastic lymphoma kinase (ALK) fusion oncogenes represent a novel molecular target in a small subset of non-small cell lung cancers (NSCLC).

This article focuses on practical considerations for the optimal management of chronic urticaria (CU) with regard to the tools and instruments that are currently available to assist in the diagnosis and assessment of this condition before and during treatment. [ABSTRACT FROM AUTHOR]

The European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA2LEN)/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 cases of CU that provide examples of how the recommendations in the guidelines can be implemented in the diagnosis of chronic spontaneous urticaria (CSU) (also called chronic idiopathic urticaria [CIU]), chronic inducible urticaria (CINDU) or CU with comorbidities. [ABSTRACT FROM AUTHOR]

Chronic urticaria ( CU), defined as the spontaneous or inducible appearance of hives, angioedema or both for 6 weeks or more, presents with a number of subtypes which all substantially impair patients' quality of life (QoL). International urticaria guidelines give clear recommendations on workup and treatment but the occurrence of CU with multiple causes and triggers (sometimes with more than one subtype occurring in a single patient) presents challenges for an individualized assessment by physicians. This review summarizes recent guidance on the classification, diagnosis and assessment of CU subtypes and discusses how currently available patient assessment tools and laboratory tests can be used in clinical practice as part of an individualized patient management plan. [ABSTRACT FROM AUTHOR]

Background In the European Union (EU), between 44 and 76 million individuals of the 217 million EU employees suffer from allergic disease of the airways or the skin. Up to 90% of these persons are untreated or insufficiently treated. This has major socio-economic consequences such as absence from work (absenteeism), particularly reduced productivity at work (presenteeism). Methods We used published literature and online statistical information from Eurostat and Eurofound to assess the costs of allergic disease to society. Results Allergies have an impact on direct, indirect, intangible and opportunity costs. Most importantly, for the EU, avoidable indirect costs per patient insufficiently treated for allergy range between €55 and €151 billion per annum due to absenteeism and presenteeism, that is, €2405 per untreated patient per year. On the other hand, appropriate therapy for allergic diseases is available at comparatively low costs at an average of €125 per patient annually, equalling only 5% of the costs of untreated disease, allowing potential savings of up to €142 billion. Conclusions A better care for allergies based on guideline-based treatment would allow Europe's economy substantial savings. In addition, allergies have an impact on learning and performance at school and university, leading to opportunity costs for society. This cannot be calculated moneywise but will have an impact in a modern knowledge-based society. Still allergies are trivialized in society, noting that the costs of therapy are paid by patients and healthcare services, whereas economic savings are made by employers and society. A change of this mindset is urgently needed. [ABSTRACT FROM AUTHOR]

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 ( GA2 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). [ABSTRACT FROM AUTHOR]

The majority of patients seeking medical advice for allergic diseases are first seen in a primary care setting. Correct diagnosis with identification of all offending allergens is an absolute prerequisite for appropriate management of allergic disease by the general practitioner. Allergy diagnostic tests recommended for use in primary care are critically reviewed in accordance with the significant workload in a primary care setting. Simplified pathways for recognition and diagnosis of allergic diseases are proposed, that should be further adapted to local (national) conditions. [ABSTRACT FROM AUTHOR]

Background Cold contact urticaria ( CCU) is characterized by itchy wheal and flare responses due to the release of histamine and other pro-inflammatory mediators after exposure to cold. The treatment of choice is nonsedating antihistamines, dosages of which may be increased up to fourfold if standard doses are ineffective. Here, we assess the effects of a standard 20 mg dose and up-dosing to 40 and 80 mg of bilastine in reducing the symptoms of CCU and inflammatory mediator release following cold challenge. Methods Twenty patients with CCU were included in this randomized, crossover, double-blind, placebo-controlled 12-week study. They received placebo, 20, 40 or 80 mg of bilastine daily each for 7 days with 14-day washout periods. The primary readout was change in critical temperature thresholds ( CTT). Secondary readouts were changes in pruritus, levels of histamine IL-6, IL-8 and TNF-α collected by skin microdialysis and safety and tolerability of bilastine. Results Bilastine 20 mg was highly effective ( P < 0.0001) in reducing CTT. Up-dosing to 80 mg significantly ( P < 0.04) increased its effectiveness. At this dose, 19 of 20 (95%) patients responded to treatment, with 12 of 20 (60%) becoming symptom free. Only one patient was refractory to treatment. Microdialysis levels of histamine, IL-6 and IL-8 assessed 1-3 h after cold challenge were significantly ( P < 0.05) decreased following up-dosing with 80 mg bilastine. Bilastine treat-ment was well tolerated without evidence of increased sedation with dose escala-tion. Conclusions Bilastine was effective in reducing the symptoms of patients with CCU. Increased efficacy of bilastine with fourfold up-dosing was without sedation and supports urticaria treatment guidelines. [ABSTRACT FROM AUTHOR]

A debate at the European Union Parliament was held on 13 November 2012 on the Impact of early diagnosis and control of chronic respiratory diseases on Active and Healthy Ageing ( AHA). The debate was held under the auspices of the Cyprus Presidency of the European Union (2012) and represents a follow-up of the priorities of the Polish Presidency of the European Union (2011). It highlighted the importance of early life events on the occurrence of chronic respiratory diseases later in life and their impact on active and healthy ageing. Epidemiologic evidence was followed by actions that should be taken to prevent and manage chronic respiratory diseases in children. The debate ended by practical, feasible and achievable projects, demonstrating the strength of the political action in the field. Three projects will be initiated from this debate: The first will be a meeting sponsored by the Région Languedoc- Roussillon on the developmental origins of chronic diseases and ageing: from research to policies and value creation. The second project is being led by the WHO Collaborating Centre for Asthma and Rhinitis: Prevention of Asthma, Prevention of Allergy ( PAPA). The third project is the GA2 LEN sentinel network. [ABSTRACT FROM AUTHOR]

Background Recently, the updated EAACI/GA2LEN/EDF/WAO guidelines for urticaria have been published. Objective To examine how chronic spontaneous urticaria (csU) patients in Germany are diagnosed and treated, and to compare the outcome to the guideline recommendations. Methods During this cross-sectional survey study, most dermatologists, paediatricians and 5149 general practitioners in private practice in Germany were asked to participate. All physicians who agreed were requested to complete a standardized questionnaire about their diagnostic and therapeutic management of csU. Results A total of 776 questionnaires were available for analysis. Most physicians (82%) were attempting to identify underlying causes in their csU patients, but with only limited success. More than 70% reported to check for total serum IgE and to do skin prick testing (not suggested in first line by guideline). In contrast, only 10% applied the autologous serum skin test. The most common first-line treatments were non-sedating antihistamines in standard or higher doses (as recommended). However, many physicians reported still using first generation sedating antihistamines (23%) (not recommended) or systemic steroids (18%). Experience with alternative options was low. Less than one-third of the participants reported to be familiar with the guidelines. Those who did, were found to be more likely to check for underlying causes, to be more experienced with antihistamine updosing and to be more reluctant to use sedating antihistamines or systemic steroids. Conclusion The diagnostic and therapeutic management of csU by private practice physicians does not sufficiently comply with the guidelines. Awareness of the guidelines can lead to improved care. [ABSTRACT FROM AUTHOR]

Background Schnitzler syndrome (SchS) is a rare disease with suspected autoinflammatory background that shares several clinical symptoms, including urticarial rash, fever episodes, arthralgia, and bone and muscle pain with cryopyrin-associated periodic syndromes ( CAPS). Cryopyrin-associated periodic syndromes respond to treatment with interleukin-1 antagonists, and single case reports of Schnitzler syndrome have shown improvement following treatment with the interleukin-1 blocker anakinra. This study evaluated the effects of the interleukin-1 antagonist rilonacept on the clinical signs and symptoms of SchS. Methods Eight patients with SchS were included in this prospective, single-center, open-label study. After a 3-week baseline, patients received a subcutaneous loading dose of rilonacept 320 mg followed by weekly subcutaneous doses of 160 mg for up to 1 year. Efficacy was determined by patient-based daily health assessment forms, physician's global assessment (PGA), and measurement of inflammatory markers including C-reactive protein ( CRP), serum amyloid A ( SAA), and S100 calcium-binding protein A12 (S100A12). Results Treatment with rilonacept resulted in a rapid clinical response as demonstrated by significant reductions in daily health assessment scores and PGA scores compared with baseline levels ( P < 0.05). These effects, which were accompanied by reductions in CRP and SAA, continued over the treatment duration. Rilonacept treatment was well tolerated. There were no treatment-related severe adverse events and no clinically significant changes in laboratory safety parameters. Conclusion Rilonacept was effective and well tolerated in patients with SchS and may represent a promising potential therapeutic option ( NCT01045772 [ Identifier]; Eudra CT #2006-004290-97). [ABSTRACT FROM AUTHOR]

Chronic urticaria (CU) is a long-lasting and distressing condition that impairs patient quality of life (QoL) by disrupting sleep and diminishing work/school productivity. Thus treatment should not only be safe and effective but also not add to this impairment or increase risks to health or safety. Non-sedating second-generation antihistamines, with their long duration of action, pharmacodynamic properties that allow once-daily dosing and lack of drug-drug interactions and sedative effects, are the first-line symptomatic treatment option, but some patients have no adequate response to standard doses of these medications. Other therapeutic approaches to refractory urticaria have been suggested but have been limited by sparse clinical data and/or significant adverse effect profiles. Although discouraged by treatment guidelines, sedating antihistamines are frequently prescribed for nighttime use when urticaria symptoms are severe as add-on therapy to a non-sedating antihistamine. However, their pronounced effects on rapid eye movement sleep and hangover negatively impact QoL, learning and performance, and limit their use for patients in occupations that require alertness. For patients who do not respond adequately to standard doses of non-sedating second-generation antihistamines, increasing the dose of non-sedating antihistamines thus may represent the safest therapeutic approach. Given the fact that only few controlled studies have assessed the efficacy and safety of high-dose non-sedating antihistamines in CU, patient safety should be a key consideration when choosing a specific antihistamine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This pocket guide is the result of a consensus reached during several GA²LEN and EAACI meetings. The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of immunotherapy in allergic rhinoconjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions of practitioners in Europe, including 'practising allergists', general practitioners and any other physicians with special interest in allergen-specific immunotherapy (SIT). It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1998 EAACI position paper, the 1998 WHO Position Paper on SIT and the 2001 Allergic Rhinitis and its Impact on Asthma (ARIA). It is also based on the ARIA update 2008 (prepared in collaboration with GA²LEN), the 'Sub-lingual Immunotherapy: WAO Position Paper 2009' (from the World Allergy Organisation) and the Methodology paper of ARIA. The recommendations cover patient selection, allergen extract to be used, route of administration of SIT (in particular, sublingual and subcutaneous immunotherapy), and necessary precautions to be followed in using SIT. [ABSTRACT FROM AUTHOR]

To cite this article: Bousquet J, Schünemann HJ, Zuberbier T, Bachert C, Baena-Cagnani CE, Bousquet PJ, Brozek J, Canonica GW, Casale TB, Demoly P, Gerth van Wijk R, Ohta K, Bateman ED, Calderon M, Cruz AA, Dolen WK, Haughney J, Lockey RF, Lötvall J, O’Byrne P, Spranger O, Togias A, Bonini S, Boulet LP, Camargos P, Carlsen KH, Chavannes NH, Delgado L, Durham SR, Fokkens WJ, Fonseca J, Haahtela T, Kalayci O, Kowalski ML, Larenas-Linnemann D, Li J, Mohammad Y, Mullol J, Naclerio R, O’Hehir RE, Papadopoulos N, Passalacqua G, Rabe KF, Pawankar R, Ryan D, Samolinski B, Simons FER, Valovirta E, Yorgancioglu A, Yusuf OM, Agache I, Aït-Khaled N, Annesi-Maesano I, Beghe B, Ben Kheder A, Blaiss MS, Boakye DA, Bouchard J, Burney PG, Busse WW, Chan-Yeung M, Chen Y, Chuchalin AG, Costa DJ, Custovic A, Dahl R, Denburg J, Douagui H, Emuzyte R, Grouse L, Humbert M, Jackson C, Johnston SL, Kaliner MA, Keith PK, Kim YY, Klossek JM, Kuna P, Le LT, Lemiere C, Lipworth B, Mahboub B, Malo JL, Marshall GD, Mavale-Manuel S, Meltzer EO, Morais-Almeida M, Motala C, Naspitz C, Nekam K, Niggemann B, Nizankowska-Mogilnicka E, Okamoto Y, Orru MP, Ouedraogo S, Palkonen S, Popov TA, Price D, Rosado-Pinto J, Scadding GK, Sooronbaev TM, Stoloff SW, Toskala E, van Cauwenberge P, Vandenplas O, van Weel C, Viegi G, Virchow JC, Wang DY, Wickman M, Williams D, Yawn BP, Zar HJ, Zernotti M, Zhong N, In collaboration with the WHO Collaborating Center of Asthma and Rhinitis (Montpellier). Development and implementation of guidelines in allergic rhinitis – an ARIA-GA2LEN paper. Allergy 2010; 65: 1212–1221. The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved. [ABSTRACT FROM AUTHOR]

To cite this article: Dölle S, Hoser D, Rasche C, Loddenkemper C, Maurer M, Zuberbier T, Worm M. Long-term reduction in local inflammation by a lipid raft molecule in atopic dermatitis. Allergy 2010; 65: 1158–1165. Background: The complex pathogenesis of atopic dermatitis (AD) is guided by cell surface receptor-mediated signal transduction regulated in lipid rafts. Miltefosine is a raft-modulating molecule targeting cell membranes. With this controlled clinical study, the clinical and immunomodulatory efficacy of miltefosine was investigated in patients with AD in comparison with a topical corticosteroid treatment. Methods: Sixteen patients with AD were treated topically with miltefosine and hydrocortisone localized on representative AD target lesions for 3 weeks. To assess the clinical efficacy, the three item severity (TIS) score was evaluated before, during and after treatment as well as after 4-week-follow-up period. To study the anti-inflammatory effect of miltefosine on the cellular T cell pattern, skin biopsies were analysed before and after treatment. Results: The TIS score dropped in both groups significantly after treatment. A carry-over effect was exclusively seen for miltefosine after discontinuing the treatment. These findings were substantiated by thermographic imaging with a significant decrease in the maximum temperature ( Tmax) after miltefosine application ( P = 0.034, ΔTmax = 1.7°C [2.1–3.9]). Immunohistochemically, a reduction in lesional CD4+-infiltrating T cells was observed in both treatments. Moreover, increased FoxP3+ cells were present in the skin after miltefosine treatment (before 5.4% [1.9–9.8], after 6.2% [3.5–9.5]). Conclusion: We demonstrate that miltefosine is locally active in patients with AD and led to a sustained clinical improvement in local skin inflammation. Moreover, the increased frequency of FoxP3+ cells in the skin of patients with AD suggests its immunomodulatory properties. [ABSTRACT FROM AUTHOR]

Background Tamoxifen (TX) represents the prototype selective oestrogen receptor modulator. In addition to its use in breast cancer, TX possesses immunomodulatory functions and displays beneficial effects in models of systemic lupus erythematosus. We hypothesized that TX might inhibit type I allergic reactions, which are also characterized by deviations in humoral immunity. Objective To evaluate the effects of TX on the allergic immune response in appropriate mouse models. Methods Balb/c mice were sensitized with ovalbumin (OVA)-alum by the intraperitoneal route, and humoral parameters, T cell cytokine patterns and OVA-induced ear swelling responses were determined in a preventive (start of TX treatment before sensitization) and a therapeutic setting (start after sensitization), respectively. In addition, the impact of TX on clinical signs, epidermal thickness and leucocyte infiltration of the skin was investigated in a model of allergen-induced dermatitis. Results Preventive TX treatment interfered with all aspects of the allergic immune response, leading to a reduction of allergen-specific Ig levels (IgE, IgG1 and IgG2a), a skewing effect in the T cell compartment with the inhibition of IL-4 and an abrogation of ear swelling responses. Interestingly, a therapeutic TX administration was also effective in reducing Ig levels and ear swelling responses. The vigorous systemic effects were additionally mirrored by local changes in allergen-dependent dermatitis with reduced clinical symptoms, diminished epidermal thickness and decreased CD4+ and CD8+ cell infiltrates. Conclusion TX inhibits allergic responses when given preventively and also therapeutically, and improves allergen-induced dermatitis. Because of its effectiveness, TX could bear significant therapeutic potential for the treatment of allergies. Cite this as: M. Babina, F. Kirn, D. Hoser, D. Ernst, W. Rohde, T. Zuberbier and M. Worm, Clinical & Experimental Allergy, 2010 (40) 1256–1265. [ABSTRACT FROM AUTHOR]

To cite this article: Braido F, Bousquet PJ, Brzoza Z, Canonica GW, Compalati E, Fiocchi A, Fokkens W, Gerth van Wijk R, La Grutta S, Lombardi C, Maurer M, Pinto AM, Ridolo E, Senna GE, Terreehorst I, Todo Bom A, Bousquet J, Zuberbier T, Baiardini I. Specific recommendations for PROs and HRQoL assessment in allergic rhinitis and/or asthma: a GA2LEN taskforce position paper. Allergy 2010; 65: 959–968. The GA2LEN taskforce on Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) published in 2009 a position paper concerning PROS and HRQoL assessment in clinical trials on allergy. Because of the specificity of this topic in asthma and rhinitis, specific recommendations are needed. The aim of this position paper is to define PROs and their meaning in asthma and rhinitis research, explore the available tools to provide criteria for a proper choice, identify patient-related factor which could influence PROs assessment, define specific recommendations for assessment, analysis and results spreading, underline the unexplored areas and unmet needs. PROs assessment is gaining increasing importance, and it must be performed with a rigorous methodological procedure and using validated tools. This approach enables to better understand patient-related factors influencing clinical trials and real-life management outcomes, identify patients subgroups that can benefit from specific treatment and management plan and tailor treatment to address PROs (not only physician-defined targets) to improve asthma and rhinitis management. [ABSTRACT FROM AUTHOR]