Patients with chronic spontaneous urticaria (CSU) are widely held to often have other autoimmune disorders, including autoimmune thyroid disease. Here, we systematically evaluated the literature on ...the prevalence of thyroid autoimmunity in CSU and vice versa. There is a strong link between CSU and elevated levels of IgG antithyroid autoantibodies (AAbs), with most of a large number of studies reporting rates of ≥10%. Levels of IgG against thyroid peroxidase (TPO) are more often elevated in CSU than those of other IgG antithyroid AAbs (strong evidence). Levels of IgG antithyroid AAbs are more often elevated in adult patients with CSU than in children (strong evidence). Patients with CSU exhibit significantly higher levels of IgG antithyroid AAbs (strong evidence) and IgE‐anti‐TPO (weak evidence) than controls. Elevated IgG antithyroid AAbs in CSU are linked to the use of glucocorticoids (weak evidence) but not to disease duration or severity/activity, gender, age, or ASST response (inconsistent evidence). Thyroid dysfunction rates are increased in patients with CSU (strong evidence). Hypothyroidism and Hashimoto's thyroiditis are more common than hyperthyroidism and Graves’ disease (strong evidence). Thyroid dysfunction is more common in adult patients with CSU than in children (strong evidence) and in female than in male patients with CSU (weak evidence). Urticaria including CSU is more prevalent in patients with thyroid autoimmunity than in controls (weak evidence). CSU can improve in response to treatment with levothyroxine or other thyroid drugs (strong evidence). Pathogenic mechanisms in CSU patients with thyroid autoimmunity may include IgE against autoantigens, immune complexes, and complement.
We fabricated flexible, transparent, and conductive metal grids as transparent conductive materials (TCM) with adjustable properties by direct nanoimprinting of self-assembling colloidal metal ...nanowires. Ultrathin gold nanowires (diameter below 2 nm) with high mechanical flexibility were confined in a stamp and readily adapted to its features. During drying, the wires self-assembled into dense bundles that percolated throughout the stamp. The high aspect ratio and the bundling yielded continuous, hierarchical superstructures that connected the entire mesh even at low gold contents. A soft sintering step removed the ligand barriers but retained the imprinted structure. The material exhibited high conductivities (sheet resistances down to 29 Ω/sq) and transparencies that could be tuned by changing wire concentration and stamp geometry. We obtained TCMs that are suitable for applications such as touch screens. Mechanical bending tests showed a much higher bending resistance than commercial ITO: conductivity dropped by only 5.6% after 450 bending cycles at a bending radius of 5 mm.
Background
Omalizumab is an effective and well‐tolerated treatment for chronic spontaneous urticaria (CSU). Markers and predictors of response are largely unknown, but needed to optimize omalizumab ...treatment. Omalizumab targets IgE, and IgE levels may be linked to the effects of treatment. We evaluated whether response rates to treatment with omalizumab in patients with CSU are linked to their baseline IgE levels, their IgE levels after omalizumab treatment, and the ratio of on treatment IgE and baseline IgE levels.
Methods
Chronic spontaneous urticaria (CSU) patients (n = 113) were treated with omalizumab 300 mg/4 weeks for 12 weeks, when their treatment responses, that is, no, partial, or complete response, were assessed by use of the urticaria activity score, physician and patient visual analog scale, and treatment effectiveness score. Total IgE levels were measured before treatment (bIgE) with omalizumab and 4 weeks thereafter (w4IgE).
Results
Nonresponders to omalizumab had significantly lower bIgE levels (17.9, 17.0‐55.0 IU/mL) than partial responders (82.0, 46.2‐126.5 IU/mL, P = .008) and complete responders (73.7, 19.45‐153.8 IU/mL, P = .032). Nonresponders also had lower w4IgE levels and lower ratios of w4IgE/bIgE levels than partial and complete responders (P < .001). Nonresponse to omalizumab was best predicted by patients' w4IgE/bIgE ratios, significantly better than by bIgE levels (P = .016).
Conclusions
In CSU, total IgE levels and their change predict the response to treatment with omalizumab. The assessment of pre‐ and post‐treatment IgE levels and their ratio may help to improve the management of CSU in patients who require omalizumab treatment.
Summary
Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle‐aged women. It usually lasts for several years (> 1 year in 25–75% of patients) and often ...takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1‐antihistamines, even at higher doses, and third‐ and fourth‐line therapies (omalizumab and ciclosporin) control the disease only in two‐thirds of H1‐antihistamine‐resistant patients. Here we review the impact of CU on different aspects of patients’ quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health‐related quality of life (HRQoL), particularly when CSU is associated with angio‐oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio‐oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients’ performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.
Plain language summary available online
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?
Himalayan glaciers supply meltwater to densely populated catchments in South Asia, and regional observations of glacier change over multiple decades are needed to understand climate drivers and ...assess resulting impacts on glacier-fed rivers. Here, we quantify changes in ice thickness during the intervals 1975-2000 and 2000-2016 across the Himalayas, using a set of digital elevation models derived from cold war-era spy satellite film and modern stereo satellite imagery. We observe consistent ice loss along the entire 2000-km transect for both intervals and find a doubling of the average loss rate during 2000-2016 -0.43 ± 0.14 m w.e. year
(meters of water equivalent per year) compared to 1975-2000 (-0.22 ± 0.13 m w.e. year
). The similar magnitude and acceleration of ice loss across the Himalayas suggests a regionally coherent climate forcing, consistent with atmospheric warming and associated energy fluxes as the dominant drivers of glacier change.
A specific net present value (SNPV) approach is introduced as a criterion in economic engineering decisions. The SNPV expresses average costs, including the growth rate and plant utilisation over the ...planning horizon, factors that are excluded from a standard net present value approach. The use of SNPV favours alternatives that are cheaper per service unit and are therefore closer to the costs that a user has to cover. It also shows that demand growth has a similar influence on average costs as an economy of scale. In a high growth scenario, solutions providing less idle capacity can have higher present value costs and still be economically favourable.
The SNPV approach is applied in two examples to calculate acceptable additional costs for modularisation and comparable costs for on-site treatment (OST) as an extreme form of modularisation. The calculations show that: (i) the SNPV approach is suitable for quantifying the comparable costs of an OST system in a different scenario; (ii) small systems with projected high demand growth rates and high real interest rates are the most probable entry market for OST water treatment systems; (iii) operating expenses are currently the main economic weakness of membrane-based wastewater OST systems; and (iv) when high growth in demand is expected, up to 100% can be additionally invested in modularisation and staging the expansion of a treatment plant.
Background
Elevated levels of C‐reactive protein (CRP), a sensitive marker of inflammation, have been consistently reported in chronic spontaneous urticaria (CSU). Here, we retrospectively analyzed ...data from 1253 CSU patients from 2 centers to answer the following questions: (i) What is the prevalence of elevated levels of CRP in CSU? (ii) Why do CSU patients show elevated levels of CRP? (iii) Are elevated CRP levels relevant?
Methods
Serum levels of CRP were measured by the nephelometric method. We collected information regarding various laboratory tests including ESR, CBC with differential, D‐dimer, fibrinogen, C3, C4, IL‐6, etc. For most patients, we also collected data on age, gender, duration of CSU, presence of angioedema, activity (UAS at the time of blood sampling and for 7 days), quality of life (CU‐Q2oL and/or DLQI), comorbidities and possible causes of CSU, and autologous serum skin test (ASST) response. The efficacy of second‐generation antihistamines was evaluated on the day of blood collecting.
Results
One‐third of CSU patients had elevated levels of CRP. Higher levels of CRP were associated with ASST positivity (P = .009) and arterial hypertension (P = .005), but not with other possible causes or comorbidities of CSU. C‐reactive protein correlated with urticaria activity (P < .001), quality of life impairment (P = .026), and inflammatory and coagulation markers (P < .001). C‐reactive protein levels were significantly higher in nonresponders to antihistamines as compared to responders (P < .001).
Conclusion
Elevated levels of CRP are common and relevant in CSU patients. The assessment of CRP levels may help to optimize the management of patients with CSU.
Summary
Chronic spontaneous urticaria (CSU) is a mast cell‐driven disease that is defined as the recurrence of weals, angioedema or both for > 6 weeks due to known or unknown causes. As of yet, ...disease diagnosis is purely clinical. Objective tools are needed to monitor the activity of CSU and the efficacy of treatment. Recently, several reports have suggested that blood parameters may be considered as potential disease‐related biomarkers. Here, we reviewed available literature on blood biomarkers for CSU diagnosis, activity monitoring, duration, patient subgroup allocation or response to treatment. We performed a PubMed, Google Scholar and Web of Science search and identified and analysed 151 reports published prior to January 2016. We found strong evidence for significant differences between patients with CSU and healthy controls in blood levels or values of D‐dimer, C‐reactive protein (CRP), matrix metalloproteinase‐9 (MMP‐9), mean platelet volume (MPV), factor VIIa, prothrombin fragment 1 + 2 (F1 + 2), tumour necrosis factor, dehydroepiandrosterone sulphate and vitamin D. Also, there is strong evidence for a significant association between CSU activity and blood levels or values of D‐dimer, F1 + 2, CRP, IL‐6 and MPV. Strong evidence for reduced basophil count and high levels of IgG anti‐FcεRI in the subgroup of CSU patients with positive autologous serum skin test was shown. In contrast, the evidence for all reported blood biomarkers for differentiating CSU from other diseases, or a role in prognosis, is weak, inconsistent or non‐existent. Taken together, we identified 10 biomarkers that are supported by strong evidence for distinguishing patients with CSU from healthy controls, or for measuring CSU activity. There is a need for further research to identify biomarkers that predict outcome or treatment response in 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.
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