Contact System Activation and Bradykinin Generation in Angioedema: Laboratory Assessment and Biomarker Utilization.

The role of contact system activation has been clearly established in the pathogenesis of hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH). C1 inhibitor (C1INH)-protease complexes, levels of functional C1INH, plasma kallikrein activation, and cleavage of high-molecular-weight kininogen have each been associated with disease activity. More recently, HAE with normal levels of C1INH (HAE-nl-C1INH) has been recognized. Six genetic mutations have been identified which are linked to HAE-nl-C1INH phenotypes. The majority of individuals with HAE-nl-C1INH fall into the unknown category. There is substantial evidence that bradykinin generation underlies the recurrent attacks of swelling in some of these cohorts.

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.

The burden of chronic spontaneous urticaria: unsatisfactory treatment and healthcare resource utilization in France (the ASSURE-CSU study).

Data on the clinical burden of chronic spontaneous urticaria (CSU) and economic consequences are lacking in France. To characterize the clinical and economic burden of CSU in symptomatic patients despite treatment by analysing data of French patients from the ASSURE-CSU study. ASSURE-CSU was an international observational study that included CSU patients with symptoms that lasted for 12 months or more despite treatment. Disease characteristics and healthcare resource use were obtained from medical records. Data on disease history, health-related quality of life (HR-QoL), and work productivity were collected from a patient survey. A total of 101 patients were analysed (76.2% female; mean age: 48.9 years) with moderate to severe disease (UAS7 score ≥16) in 43.4% and angioedema in 72.3%. The mean (S.D.) total scores of Chronic Urticaria Quality of Life (CU-Q2oL) and Dermatology Life Quality Index (DLQI) were 37.7 (22.3) and 9.7 (6.9), respectively, thus indicating a significant impact of the disease on HR-QoL. Mean absenteeism and presenteeism were 6.4% and 20.8%, respectively, with a mean loss of work productivity estimated at 20.7%. The mean (S.D.) total direct cost of CSU was €2,397 per patient per year and was mainly driven by therapies (€1,435) and inpatient costs (€859). The indirect costs for four weeks were mainly presenteeism (€421) and loss of work productivity (€420). CSU significantly impairs HR-QoL, which increases with the severity of the disease. The direct and indirect costs for the management of symptomatic CSU are an important economic burden.

A practical, clinical approach to the assessment and management of suspected insulin allergy.

BACKGROUND: Although allergic reactions to insulin are uncommon, they can be difficult to diagnose and management may be very difficult in subjects with Type 1 diabetes with severe allergy. Access to allergists and specialist diagnostic tests is limited and few diabetes specialists are familiar with desensitization as a means of treating allergy. People with diabetes may develop symptoms which mimic insulin allergy but are attributable to other conditions. CASE REPORTS: Here we describe three cases of insulin allergy. One patient presented with severe, albeit localized, urticarial reactions at injection sites. The most severe case was a woman with recent-onset Type 1 diabetes who presented with grade 2 anaphylaxis. The third patient presented with generalized urticaria and angioedema. Insulin allergy was confirmed in all three cases. METHODS: Assessment involved measurement of immunoglobulin and anti-insulin antibody levels. Skin testing was performed in two cases. Treatments included desensitization in one case, alternative insulin preparations, antihistamines and continuous subcutaneous insulin infusion. In all three cases of insulin allergy there has been successful resolution of symptoms. CONCLUSIONS: The clinical assessment and investigation in cases of suspected insulin allergy is described, along with detailed algorithms for skin testing and desensitization. This case series demonstrates an approach to challenging cases of suspected insulin allergy which will be helpful for diabetes specialists.

Angioedema--assessment and treatment.

BACKGROUND: Angioedema has numerous hereditary, acquired and iatrogenic causes. A number of studies show that angioedema is inadequately assessed and treated during its acute phase as well as in the follow-up period. We present an algorithm for the assessment and treatment of patients with angioedema. KNOWLEDGE BASE: The article is based on a literature search in PubMed, a review of bibliographies and the authors' clinical experience and research. RESULTS: The majority of angioedema patients have accompanying urticaria. Pathophysiologically, angioedemas are divided into histaminergic and non-histaminergic forms. In a large group of patients no positive trigger is identified. On assessment in hospital the most frequently identified cause is drug intake, normally angiotensin-converting-enzyme inhibitors and NSAIDs , while allergic/pseudoallergic and idiopathic reactions are more commonly seen in general practice. There are a number of rare causes of angioedema, all of which are important to keep in mind. The acute and prophylactic treatment will depend on the subtype of angioedema and is best provided through cross-disciplinary collaboration. INTERPRETATION: Angioedema is a potentially life-threatening condition and should be assessed and treated systematically. It is important to remember that angioedema is either histaminergic or non-histaminergic, as the treatment of the two types is different.

[Contribution of anamnesis and clinical examination in the assessment of chronic urticaria]. / Apport de l'interrogatoire et de l'examen clinique dans le bilan d'une urticaire chronique.

Chronic urticaria is defined as an eruption of oedematous and pruriginous papules, localized or widespread, evolving for more than 6 weeks. Cutaneous lesions occurs daily or recurs with remissions of a few days at a few weeks. Diagnosing chronic urticaria is easy, but to find an etiology is much more tiresome. This is why a detailed anamnesis and a clinical examination are significant elements in the assessment of chronic urticaria. The analysis of the literature according to criteria's of the National Agency of Accreditation and Evaluation in Health shows that the anamnesis and the clinical examination are sufficient to carry a diagnosis in the majority of physical urticaria. However, they bring elements to suspect an urticarial vasculitis, a systemic disease or another etiology, allowing orientation of complementary examinations. The anamnesis permits to detect worsening factors, in particular drugs and/or food, their suppression leading to an improvement of symptomatology.

Assessment of urticaria and angio-oedema.

There are many types of urticaria and the principal form of assessment is by clinical history and examination. Urticarial weal formation involves acute, reversible vasodilatation and increased vascular permeability. If the process is deeper the more diffuse swelling is termed angio-oedema. The major types of urticaria include allergic, physical and idiopathic forms. In allergic urticaria, IgE-mediated degranulation of mast cells results in weals of short duration which typically respond well to antihistamines. Physical urticarias are induced by physical insults including pressure, scratch, cold, etc. The distribution and duration of individual weals may suggest the causal factor. Chronic idiopathic urticaria can be very variable, with individual weals lasting between 90 min and 24 hours. Longer-lasting weals are less responsive to anti-histamines and clearly involve other mediators. When long-lasting weals fade leaving a bruised appearance urticarial vasculitis is present which may only respond to systemic corticosteroids. In a proportion of individuals with chronic idiopathic urticaria, auto-antibodies are present with specificity for the high affinity receptor for IgE or sometimes, for IgE itself. In general laboratory tests for allergic factors or other assessments of general health are completely unhelpful.