Chronic urticaria in the real-life clinical practice setting in the UK: results from the noninterventional multicentre AWARE study.

BACKGROUND: Chronic urticaria (CU) is a skin condition characterized by repeated occurrence of itchy weals and/or angio-oedema for > 6 weeks. AIM: To provide data demonstrating the real-life burden of CU in the UK. METHODS: This UK subset of the worldwide, prospective, noninterventional AWARE study included patients aged 18-75 years diagnosed with H1-antihistamine (H1-AH)-refractory chronic spontaneous urticaria (CSU) for > 2 months. Baseline characteristics, disease activity, treatments, comorbidities and healthcare resource use were documented. Quality of life (QoL), work productivity and activity impairment were assessed. RESULTS: Baseline analysis included 252 UK patients. Mean age and body mass index were 45.0 years and 29.0 kg/m2 , respectively. Most patients were female (77.8%) and had moderate/severe disease activity (mean Urticaria Activity Score over 7 days was 18.4) and a 'spontaneous' component to their CU (73.4% CSU; 24.6% CSU and chronic inducible urticaria). Common comorbidities included depression/anxiety (24.6%), asthma (23.8%) and allergic rhinitis (12.7%). A previous treatment was recorded for 57.9% of patients. Mean Dermatology Life Quality Index score was 9.5, and patients reported impairments in work productivity and activity. Healthcare resource use was high. Severity of CSU was associated with female sex, obesity, anxiety and diagnosis. Only 28.5% of patients completed all nine study visits, limiting analysis of long-term treatment patterns and disease impact. CONCLUSIONS: Adult H1-AH-refractory patients with CU in the UK reported high rates of healthcare resource use and impairment in QoL, work productivity and activity at baseline. The differing structures of UK healthcare may explain the high study discontinuation rates versus other countries.

Angioedema in chronic spontaneous urticaria is underdiagnosed and has a substantial impact: Analyses from ASSURE-CSU.

BACKGROUND: ASSURE-CSU revealed differences in physician and patient reporting of angioedema. This post hoc analysis was conducted to evaluate the actual rate of angioedema in the study population and explore differences between patients with and without angioedema. METHODS: This international observational study assessed 673 patients with inadequately controlled chronic spontaneous urticaria (CSU). Physicians abstracted angioedema data from medical records, which were compared with patient-reported data. Patients in the Yes-angioedema category had angioedema reported in the medical record and a patient-reported source. For those in the No-angioedema category, angioedema was reported in neither the medical record nor a patient-reported source. Those in the Misaligned category had angioedema reported in only one source. Statistical comparisons between Yes-angioedema and No-angioedema categories were conducted for measures of CSU activity, health-related quality of life (HRQoL), productivity and healthcare resource utilization (HCRU). Regression analyses explored the relationship between Dermatology Life Quality Index (DLQI) score and angioedema, adjusting for important covariates. RESULTS: Among evaluable patients, 259 (40.3%), 173 (26.9%) and 211 (32.8%) were in the Yes-angioedema, No-angioedema and Misaligned category, respectively. CSU activity and impact on HRQoL, productivity, and HCRU was greater for Yes-angioedema patients than No-angioedema patients. After covariate adjustment, mean DLQI score was significantly higher (indicating worse HRQoL) for patients with angioedema versus no angioedema (9.88 vs 7.27, P < .001). The Misaligned category had similar results with Yes-angioedema on all outcomes. CONCLUSIONS: Angioedema in CSU seems to be under-reported but has significant negative impacts on HRQoL, daily activities, HCRU and work compared with no angioedema.

National clinical practice guidelines for allergen immunotherapy: An international assessment applying AGREE-II.

BACKGROUND: Since 1988, numerous allergen immunotherapy guidelines (AIT-GLs) have been developed by national and international organizations to guide physicians in AIT. Even so, AIT is still severely underused. OBJECTIVE: To evaluate AIT-GLs with AGREE-II, developed in 2010 by McMaster University methodologists to comprehensively evaluate GL quality. METHODS: Allergist, from different continents, knowledgeable in AIT and AGREE-II trained were selected into the project team. The project received methodologists' guidance. AIT-GLs in any language were sought from 1980 to 2016; AIT-GLs were AGREE II-evaluated by at least 2 team members, independently; discrepancies were resolved in a second round, by team discussion or methodologists' consulting. RESULTS: We found 31 AIT-GLs (15 post-2010), ranging from local consensus reports to international position papers (EAACI, AAAAI-ACAAI, WAO). Pre-2010 GLs scored 1.6-4.6 (23%-67%) and post-2010 GLs scored 2.1-6 (30%-86%), on a 7-point Likert scale. The highest scores went to: German-Austrian-Swiss (6.0), Mexican (5.1), and the AAAAI/ACAAI AIT-GL (4.7). These were also the only 3 GLs that received "yes" of both evaluators to the item: "I would recommend this GL for use." The domains of "Stakeholder involvement" and "Rigor of Development" only scored 3/7, and "Applicability" scored the lowest. Strikingly, newer GLs only scored clearly better in "Editorial independence" and "Global evaluation." CONCLUSIONS: In AIT-GLs, there is still a lot of room for improvement, especially in domains crucial for the dissemination. For some GLs, the "Scientific rigor" domain flawed. When resources are limited, transculturizing a high-quality GL might be preferable over developing a GL from zero. Our study and AGREE-II could help to select the best candidate. CLINICAL IMPLICATIONS: We here evaluate allergen immunotherapy guideline (AIT-GL) quality. Only high-quality AIT-GLs should be consulted for AIT management decisions. In low-resource settings, transculturization of these is preferred over developing low-quality guidelines.

The burden of chronic spontaneous urticaria is substantial: Real-world evidence from ASSURE-CSU.

BACKGROUND: Chronic spontaneous urticaria (CSU) can be debilitating, difficult to treat, and frustrating for patients and physicians. Real-world evidence for the burden of CSU is limited. The objective of this study was to document disease duration, treatment history, and disease activity, as well as impact on health-related quality of life (HRQoL) and work among patients with inadequately controlled CSU, and to describe its humanistic, societal, and economic burden. METHODS: This international observational study assessed a cohort of 673 adult patients with CSU whose symptoms persisted for ≥12 months despite treatment. Demographics, disease characteristics, and healthcare resource use in the previous 12 months were collected from medical records. Patient-reported data on urticaria and angioedema symptoms, HRQoL, and work productivity and activity impairment were collected from a survey and a diary. RESULTS: Almost 50% of patients had moderate-to-severe disease activity as reported by Urticaria Activity Score. Mean (SD) Dermatology Life Quality Index and Chronic Urticaria Quality of Life Questionnaire scores were 9.1 (6.62) and 33.6 (20.99), respectively. Chronic spontaneous urticaria markedly interfered with sleep and daily activities. Angioedema in the previous 12 months was reported by 66% of enrolled patients and significantly affected HRQoL. More than 20% of patients reported ≥1 hour per week of missed work; productivity impairment was 27%. These effects increased with increasing disease activity. Significant healthcare resources and costs were incurred to treat CSU. CONCLUSIONS: Chronic spontaneous urticaria has considerable humanistic and economic impacts. Patients with greater disease activity and with angioedema experience greater HRQoL impairments.

Clinical approach on challenge and desensitization procedures with aspirin in patients with ischemic heart disease and nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Hypersensitivity to acetylsalicylic acid (ASA) constitutes a serious problem for subjects with coronary artery disease. In such subjects, physicians have to choose the more appropriate procedure between challenge and desensitization. As the literature on this issue is sparse, this study aimed to establish in these subjects clinical criteria for eligibility for an ASA challenge and/or desensitization. METHODS: Collection and analysis of data on ASA challenges and desensitizations from 10 allergy centers, as well as consensus among the related physicians and an expert panel. RESULTS: Altogether, 310 subjects were assessed; 217 had histories of urticaria/angioedema, 50 of anaphylaxis, 26 of nonimmediate cutaneous eruptions, and 17 of bronchospasm related to ASA/nonsteroidal anti-inflammatory drugs (NSAID) intake. Specifically, 119 subjects had index reactions to ASA doses lower than 300 mg. Of the 310 subjects, 138 had an acute coronary syndrome (ACS), 101 of whom underwent desensitizations, whereas 172 suffered from a chronic ischemic heart disease (CIHD), 126 of whom underwent challenges. Overall, 163 subjects underwent challenges and 147 subjects underwent desensitizations; 86 of the latter had index reactions to ASA doses of 300 mg or less. Ten subjects reacted to challenges, seven at doses up to 500 mg, three at a cumulative dose of 110 mg. The desensitization failure rate was 1.4%. CONCLUSIONS: In patients with stable CIHD and histories of nonsevere hypersensitivity reactions to ASA/NSAIDs, an ASA challenge is advisable. Patients with an ACS and histories of hypersensitivity reactions to ASA, especially following doses lower than 100 mg, should directly undergo desensitization.

Drug allergy passport and other documentation for patients with drug hypersensitivity - An ENDA/EAACI Drug Allergy Interest Group Position Paper.

The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation.

In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper.

Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis.

Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review.

Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n = 12) and other nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 8), and IR to biologics (n = 3). We reported two genomewide association studies and four case-control studies on candidate genes validated by replication. Genes involved in IR to beta-lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA-DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membrane-spanning 4A gene family, histamine production pathway, and pro-inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene-gene interactions, and contrasted situations of environmental exposure.

THE SEARCH OF COMPOUNDS WITH ANTIAGGREGATION ACTIVITY AMONG S-ESTERS OF THIOSULFONIC ACIDS.

According to the current understanding, the hyperactivation of platelets may lead to increased intravascular coagulation and thrombosis. Today a relevant issue is the search for new anti-thrombotic agents that are able to modulate the activity of platelet receptors, thus, influence the processes of activation and aggregation of platelets. The aim of this study was to investigate the effects of newly synthesized thiosulfonate derivatives on platelet aggregation. The activity of the compounds was tested in vitro using platelet-rich plasma. As a result of the screening test, structural formulas of four agents with high antiaggregative activity were established. These compounds inhibited ADP- and collagen-induced platelet aggregation in a dose-dependent manner. Two of these compounds were shown to be more effective inhibitors of aggregation induced by ADP (IC50 - 8-10 µM), as well as collagen (IC50 - 1.5-2.0 µM).

Immediate hypersensitivity to chlorhexidine is increasingly recognised in the United Kingdom

BACKGROUND: Chlorhexidine is widely used as an antiseptic agent. It is a potentially allergenic substance that can cause severe hypersensitivity reactions. OBJECTIVE: We describe six patients who had anaphylactic reactions attributed to chlorhexidine during surgery. These patients were exposed to chlorhexidine in gels, swabs and catheters. MATERIALS AND METHODS: Six patients from three UK centres with clinical history suggestive of anaphylaxis during surgery are reported. Detailed history, review of case notes, determination of chlorhexidine specific IgE, mast cell tryptase and skin tests were performed. RESULTS: On detailed assessment five of six patients demonstrated a previous history of reactions on re-exposure to chlorhexidine. All six patients had elevated specific IgE to chlorhexidine. Skin prick test with chlorhexidine was performed in four of the six patients and was found to be positive. CONCLUSION: Immediate hypersensitivity to chlorhexidine appears to be common but underreported in the UK. We recommend that centres investigating patients with reactions during anaesthesia and surgery should routinely include testing for chlorhexidine allergy

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Immediate hypersensitivity to chlorhexidine is increasingly recognised in the United Kingdom.

BACKGROUND: Chlorhexidine is widely used as an antiseptic agent. It is a potentially allergenic substance that can cause severe hypersensitivity reactions. OBJECTIVE: We describe six patients who had anaphylactic reactions attributed to chlorhexidine during surgery. These patients were exposed to chlorhexidine in gels, swabs and catheters. MATERIALS AND METHODS: Six patients from three UK centres with clinical history suggestive of anaphylaxis during surgery are reported. Detailed history, review of case notes, determination of chlorhexidine specific IgE, mast cell tryptase and skin tests were performed. RESULTS: On detailed assessment five of six patients demonstrated a previous history of reactions on re-exposure to chlorhexidine. All six patients had elevated specific IgE to chlorhexidine. Skin prick test with chlorhexidine was performed in four of the six patients and was found to be positive. CONCLUSION: Immediate hypersensitivity to chlorhexidine appears to be common but underreported in the UK. We recommend that centres investigating patients with reactions during anaesthesia and surgery should routinely include testing for chlorhexidine allergy.