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Purpose of Review: Intranasal corticosteroid sprays have been available as over-the-counter (OTC) medications since 2013. As such, clinicians need to be up-to-date with the risks and the safety of INS, as patients may have concerns and detailed questions. The following is a review of the recent medical literature regarding the safety profile, adverse reactions, and special populations using INS., Recent Findings: The latest research on intranasal steroid sprays (INS) continue to confirm that INS rarely have significant local side effects, such as severe and persistent epistaxis. Recent studies looking at systemic side effects such as hypothalamic pituitary axis suppression, growth effects, and ocular effects do not indicate any new concerns nor have found significant differences from the past literature. The use of combination INS and topical antihistamine medications did not reveal any new safety issues. Use of INS with topical decongestants found some limited effects of tachyphylaxis and rebound congestion. Studies continue to support the use of newer INS for children and continued monitoring of growth in this population. The HIV population should avoid use of INS with the prescription of ritonavir, given demonstration of adrenal suppression. This updated perspective has found that newer generation INS should be used at the lowest effective dose for the selected population, that clinicians can inform patients using the OTC INS preparations that there are very few safety concerns, and that regular follow-up visits can provide further reassurance with physical examinations and address patient's questions. Future research regarding the safety of INS should study newer preparations when developed and if used in combination with other topical agents.

Purpose: To determine the effect of mycophenolate mofetil (MMF) on retinal degeneration on two mouse models of retinitis pigmentosa., Methods: Intraperitoneal injections of MMF were administered daily in rd10 and c57 mice starting at postoperative day 12 (P12) and rd1 mice starting at P8. The effect of MMF was assessed with optical coherence tomography, immunohistochemistry, electroretinography, and OptoMotry. Whole retinal cyclic guanosine monophosphate (cGMP) and mycophenolic acid levels were quantified with mass spectrometry. Photoreceptor cGMP cytotoxicity was evaluated with cell counts of cGMP immunostaining., Results: MMF treatment significantly delays the onset of retinal degeneration and cGMP-dependent photoreceptor cytotoxicity in rd10 and rd1 mice, albeit a more modest effect in the latter. In rd10 mice, treatment with MMF showed robust preservation of the photoreceptors up to P22 with associated suppression of cGMP immunostaining and microglial activation; The neuroprotective effect diminished after P22, but outer retinal thickness was still significantly thicker by P35 and OptoMotry response was significantly better up to P60. Whereas cGMP immunostaining of the photoreceptors were present in rd10 and rd1 mice, hyperphysiological whole retinal cGMP levels were observed only in rd1 mice., Conclusions: Early treatment with MMF confers potent neuroprotection in two animal models of RP by suppressing the cGMP-dependent common pathway for photoreceptor cell death. The neuroprotective effect of MMF on cGMP-dependent cytotoxicity occurs independently of the presence of hyperphysiological whole retinal cGMP levels. Thus our data suggest that MMF may be an important new class of neuroprotective agent that could be useful in the treatment of patients with RP.

Background: The international guideline for urticaria recommends the use of the Urticaria Activity Score 7 (UAS7) and the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) to assess patients with chronic spontaneous urticaria (CSU) for their disease activity and impact on quality of life, respectively. Over the last decade, both tools have been validated in many different languages but not in Arabic., Objective: To validate the Arabic UAS7 and CU-Q2oL in patients with CSU in Lebanon., Methods: After a structured translation process of both instruments into Arabic, their construct and known-groups validity as well as internal consistency reliability were tested in a longitudinal prospective study using a cluster sample of 152 Lebanese CSU patients. The study also included a repetitive administration of both instruments in 2-week intervals in 44 patients in order to assess their test-retest reliability., Results: Both the Arabic UAS7 and CU-Q2oL demonstrated high internal consistency (Cronbach alpha of 0.95 and 0.82, respectively) and moderate-to-high test-retest reliability (intraclass coefficient of 0.61 and 0.91, respectively). Exploratory factor analysis of the Arabic CU-Q2oL revealed five components that explained 81.8% of the total variance. Significant correlations were found between the Arabic CU-Q2oL and the Dermatology Life Quality Index (DLQI) (r = 0.86) and mild-to-moderate correlations between the Arabic UAS7 and CU-Q2oL (r = 0.52) as well as the DLQI (r = 0.51)., Conclusions: Our findings demonstrate that the Arabic versions of the UAS7 and the CU-Q2oL are valid and reliable patient-reported outcome measures in patients with CSU in Lebanon., (© 2020 the International Society of Dermatology.)

Background: Recurrent angioedema (RA) is an important clinical problem in routine care and emergency medicine. As of recently, the only validated tools to specifically assess disease status in patients with RA were diary-type activity assessments and angioedema-related quality-of-life questionnaires. Although these tools are particularly helpful in clinical studies, they were not designed to determine disease control or to guide treatment decisions. To close this gap, the Angioedema Control Test (AECT) was published recently., Objective: To test the AECT for its validity and reliability, and to identify a cutoff value to aid treatment decisions., Methods: Two AECT versions with a recall period of 4 weeks (AECT-4wk) and 3 months (AECT-3mo) were tested for their internal consistency and test-retest reliability, convergent and known-groups validity as well as screening accuracy in 81 patients with RA with bradykinin-mediated angioedema, mast cell mediator-mediated angioedema, or idiopathic angioedema., Results: Both AECT versions showed excellent internal consistency reliability with a Cronbach alpha value of more than 0.85 and test-retest reliability with an intraclass correlation coefficient greater than 0.9. The convergent validity of both AECT versions was high. Both tools showed strong correlations with anchors of disease control, angioedema frequency, and health-related quality of life. A stratification of AECT scores into different levels of disease control together with a receiver-operating characteristic curve analysis suggested a cutoff value of 10 or more points to identify patients with well-controlled RA versus less than 10 points to identify patients with poorly controlled disease for both AECT versions., Conclusions: The AECT is the first valid and reliable patient-reported outcome measure to assess disease control in patients with RA., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The urticaria control test (UCT) is a patient-reported outcome measure designed to determine the current level of disease control in patients with chronic urticaria (CU). Recently, a Brazilian UCT was developed, but its validity and reliability are unknown. Method: The clinimetric properties of the Brazilian UCT short form (UCTsh) and its long form (UCTlg) were determined in 130 patients with CU. In parallel, the urticaria activity scores (UAS) that covers 7 days (UAS7) and 28 days (UAS28) were used to assess disease activity. Subsequently, the results were analyzed statistically to determine the validity, reliability, and interpretability of the Brazilian UCT versions. Results: A total of 107 female (82%) and 23 male patients with CU completed both versions of the Brazilian UCT. Both of the Brazilian UCT versions showed excellent internal consistency reliability. In addition, the Brazilian UCT results showed strong correlations with UAS7 and UAS28 results, which indicated high levels of convergent validity. The test-retest reliability was examined in a subsample of 27 patients with CU and was found to be excellent. Notably, the results of both Brazilian UCT versions correlated extensively, which suggested that the UCTsh can replace the UCTlg without changing the UCT results. Conclusion: The Brazilian UCT is a valid and reliable tool for assessing disease control. To facilitate the use of the Brazilian UCT in global studies and to put a stronger focus on the specificity, we propose that the same cutoff values for well-controlled disease should be used as identified in the original publication of the UCT, i.e., ≥12 points for the UCTsh.

Background: Recurrent angioedema (AE) is an important clinical problem in the context of chronic urticaria (mast cell mediator-induced), ACE-inhibitor intake and hereditary angioedema (both bradykinin-mediated). To help patients obtain control of their recurrent AE is a major treatment goal. However, a tool to assess control of recurrent AE is not yet available. This prompted us to develop such a tool, the Angioedema Control Test (AECT)., Methods: After a conceptional framework was developed for the AECT, a list of potential AECT items was generated by a combined approach of patient interviews, literature review and expert input. Subsequent item reduction was based on impact analysis, inter-item correlation, additional predefined criteria for item performance, and a review of the item selection process for content validity. Finally, an instruction section was generated, and an US-American-English version was developed by a structured translation process., Results: A 4-item AECT with recall periods of 4 weeks and 3 months was developed based on 106 potential items tested in 97 patients with mast cell mediator-induced (n = 49) or bradykinin-mediated recurrent AE (n = 48). Eighty-four items were excluded based on impact analysis. The remaining 22 items could be further reduced by a method-mix of inter-item correlation, additional predefined criteria for item performance and review for content validity., Conclusions: The AECT is the first tool to assess disease control in recurrent AE patients. Its retrospective approach, its brevity and its simple scoring make the AECT ideally suited for clinical practice and trials. Its validity and reliability need to be determined in future independent studies., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Psoriasis is a prevalent skin disease that impairs multiple domains of quality of life (QoL). Pruritus, a common symptom in patients with psoriasis, may directly affect sleep, but studies investigating this are limited. We investigated the relationships between pruritus and sleep in 104 in-patients with psoriasis, who underwent dermatological assessment and completed questionnaires to determine psoriasis severity, pruritus intensity, sleep quality, QoL (skin disease-specific and generic), depressive mood and anxiety. In total, 80% of patients reported pruritus, and 39% had sleep disturbances, most commonly awakenings during sleep (33%) and sleepiness during the daytime (30%). Sleep impairment was more frequent in patients with pruritus, who had more difficulty falling asleep (P = 0.031). Overall, 14% of all patients and 34% of the patients who reported sleep disturbances reported that their sleep problems were caused by pruritus. Patients who reported sleep disturbances had lower generic QoL. Pruritus in patients with psoriasis was frequent and relevant, as evidenced by the higher rate of sleep problems in this patient group, and it was linked to a lower QoL.

Background and Objectives: Urticaria is a frequent skin condition, but reliable prevalence estimates from population studies particularly of the chronic form are scarce. The objective of this study was to systematically evaluate and summarize the prevalence of chronic urticaria by evaluating population-based studies worldwide., Methods: We performed a systematic search in PUBMED and EMBASE for population-based studies of cross-sectional or cohort design and studies based on health insurance/system databases. Risk of bias was assessed using a specific tool for prevalence studies. For meta-analysis, we used a random effects model., Results: Eighteen studies were included in the systematic evaluation and 11 in the meta-analysis including data from over 86 000 000 participants. Risk of bias was mainly moderate, whereas the statistical heterogeneity (I 2 ) between the studies was high. Asian studies combined showed a higher point prevalence of chronic urticaria (1.4%, 95%-CI 0.5-2.9) than those from Europe (0.5%, 0.2-1.0) and Northern American (0.1%, 0.1-0.1). Women were slightly more affected than men, whereas in children < 15 years we did not find a sex-specific difference in the prevalence. The four studies that examined time trends indicated an increasing prevalence of chronic urticaria over time., Conclusions: On a global level, the prevalence of chronic urticaria showed considerable regional differences. There is a need to obtain more sex-specific population-based and standardized international data particularly for children and adolescents, different chronic urticaria subtypes and potential risk and protective factors., (© 2019 The Authors. Allergy published by John Wiley & Sons Ltd.)

Introduction: Flare reactions arise due to the release of vasodilators from sensory nerves caused by antidromic transmission of action potentials after the induction of itch., Objective: We investigated the link between flare and itch using 3 models of itch., Methods: Skin provocations with histamine, capsaicin, and cowhage were performed in 31 subjects. Itch was quantified using the visual analog scale. Flare was assessed using laser speckle contrast imaging (LSCI) and digital photography., Results: The duration, intensity, and area under the curve of histamine-induced itch correlated with the area of increased blood flow measured with LSCI (r = 0.545, p = 0.002; r = 0.575, p = 0.001; and r = 0.649, p < 0.001, respectively). Itch and skin blood flow in response to capsaicin or cowhage did not correlate., Conclusion: In histamine-induced skin inflammation, itch and increased blood flow are linked. Thus, the area of histamine-induced flare may be used as a surrogate marker for histamine-induced itch., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

This update on chronic urticaria (CU) focuses on the prevalence and pathogenesis of chronic spontaneous urticaria (CSU), the expanding spectrum of patient-reported outcome measures (PROMs) for assessing CU disease activity, impact, and control, as well as future treatment options for CU. This update is needed, as several recently reported findings have led to significant advances in these areas. Some of these key discoveries were first presented at past meetings of the Collegium Internationale Allergologicum (CIA). New evidence shows that the prevalence of CSU is geographically heterogeneous, high in all age groups, and increasing. Several recent reports have helped to better characterize two endotypes of CSU: type I autoimmune (or autoallergic) CSU, driven by IgE to autoallergens, and type IIb autoimmune CSU, which is due to mast cell (MC)-targeted autoantibodies. The aim of treatment in CU is complete disease control with absence of signs and symptoms as well as normalization of quality of life (QoL). This is best monitored by the use of an expanding set of PROMs, to which the Angioedema Control Test, the Cholinergic Urticaria Quality of Life Questionnaire, and the Cholinergic Urticaria Activity Score have recently been added. Current treatment approaches for CU under development include drugs that inhibit the effects of signals that drive MC activation and accumulation, drugs that inhibit intracellular pathways of MC activation and degranulation, and drugs that silence MCs by binding to inhibitory receptors. The understanding, knowledge, and management of CU are rapidly increasing. The aim of this review is to provide physicians who treat CU patients with an update on where we stand and where we will go. Many questions and unmet needs remain to be addressed, such as the development of routine diagnostic tests for type I and type IIb autoimmune CSU, the global dissemination and consistent use of PROMs to assess disease activity, impact, and control, and the development of more effective and well-tolerated long-term treatments for all forms of CU., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: Cholinergic urticaria (CholU) is a frequent type of chronic inducible urticaria. Symptomatic treatment with second-generation antihistamines (sgAH) is recommended by current guidelines as first-line therapy, but little is known about how patients with CholU are treated in real life and how they respond to treatment., Aim: To assess real-life treatment of CholU in German-speaking countries., Methods: Patients with CholU (n = 111) took part in an online survey study that assessed their treatments and their treatment responses., Results: Virtually all patients (97 %) had used antihistamines, 87 % of them sgAH; 23 % had also taken first-generation antihistamines (fgAH). The proportion of patients who benefited from standard-dosed antihistamine treatment was low (sgAH: 32 % vs. fgAH: 16 %), and side effects of sgAH and fgAH were comparable. Updosing of antihistamines had been tried by 66 patients (59 %) (most commonly [98 %, n = 65] with sgAH) and resulted in marginally better responses (sgAH: 38 % vs. fgAH: 32 %). Only very few patients had used other treatments, mostly corticosteroids (30 %) and omalizumab (5 %)., Conclusions: SgAH were commonly used, but insufficient in about two thirds of CholU patients. Accordingly, improved use of third-line and fourth-line treatment options and development of better therapies for patients with CholU are needed., (© 2019 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

The Angioedema Activity Score (AAS) is recommended by the EAACI/GA 2 LEN/EDF/WAO guidelines for urticaria as the standard measure for assessing disease activity in patients with recurrent angioedema (RAE). To date, it has been translated into 80 languages for use in 52 countries, but it has not been formally validated in Asian patient populations. As RAE may be different in Asian and non-Asian patients, it is important to validate and characterize the reliability of tools to assess RAE disease activity in Asian patients. This study proposed to demonstrate the validity and reliability of the AAS in Asian patients. Accordingly, this study aimed to generate and validate the Thai version of the AAS and to characterize its reliability in Asian patients, specifically in Thailand. A structured translation was conducted with approval from the original authors. The Patient Global Assessment of Disease Activity (PGA-DA) was used as an instrument to compare with the Thai version of the AAS. In total, 86 patients with RAE participated in the study. Seventy-six (88%) patients had RAE with chronic spontaneous urticaria. The Thai AAS was found to be a valid and reliable instrument, with high convergent and known-groups validities, excellent internal consistency, and good test-retest reliability. The validity and reliability of the AAS for assessing RAE disease activity in Asian patients have been demonstrated by our study, making it the first to do so. This will help promote the use of the AAS, in clinical trials and practice, in Asia. It will also facilitate the comparison of disease activity in patients with RAE inside and outside Asia in future studies. However, a limitation of this study was its small number of patients., Competing Interests: Drs. Maurer and Weller report institutional research funding and personal fees for consulting from MOXIE, the AAS copyright holder. The other authors declare no conflicts of interest., (Copyright © 2019 Kanokvalai Kulthanan et al.)

Background: The Angioedema Quality of Life (AE-QoL) is the first patient reported outcome measure developed for the assessment of quality of life (QoL) impairment in patients with recurrent angioedema (RAE). This study aimed to evaluate the clinimetric properties of the AE-QoL in Thai patients and to establish categories of QoL impairment assessed by the AE-QoL., Methods: The validated Thai version of the Dermatology Life Quality Index (DLQI) and Patient Global Assessment of Quality of Life (PGA-QoL) were used to comparatively evaluate the Thai version of AE-QoL. Spearman correlations between the Thai AE-QoL and two other standard measurements (DLQI and PGA-QoL) were investigated to determine convergent validity. The Thai DLQI and PGA-QoL were used to categorize patients according to their QoL. Known-group validity of the Thai AE-QoL was later analyzed. The reliability of the Thai AE-QoL was investigated using Cronbach's alpha and intraclass correlation. Three different approaches including the distribution method, receiver operating characteristic curve analysis, and the anchor based-method were used for the interpretability., Results: A total of 86 patients with RAE with a median age of 38.0 ± 15.1 years (range 18-76) were enrolled. Of those, 76 patients (88%) had RAE with concomitant wheals, and 10 patients (11.6%) had RAE only. The AE-QoL assessed RAE-mediated QoL impairment with high convergent validity and known-groups validity, high internal consistency and test-retest reliability, and good sensitivity to change. Although the AE-QoL did not differentiate between patients with moderate and large effect as measured by PGA-QoL or DLQI in this study, AE-QoL total values of 0-23, 24 to 38, and ≥ 39 could define patients with "no effect", "small effect", and "moderate to large effect" of RAE on their QoL, respectively., Conclusions: This study supports the validity and reliability of the Thai version of the AE-QoL, which is a very different language from the original version. Categories allow to classify the effect of RAE on patients' QoL as "none", "small", and "moderate to large". Further studies are needed to confirm the applicability of AE-QoL in other Asian populations".

The development of core outcome sets (COSs; ie, a minimum set of core outcomes that should be measured and reported in all trials or in clinical practice for a specific condition) in dermatology is increasing in pace. A total of 44 dermatology-related COS projects have been registered in the online Core Outcome Measures in Effectiveness Trials database (http://www.comet-initiative.org/studies/search) and include studies on 26 different skin diseases. With the increasing number of COSs in dermatology, care is needed to ensure the delivery of high-quality COSs that meet quality standards when using state-of-the-art methods. In 2015, the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) was established. CS-COUSIN is an international, multidisciplinary working group aiming to improve the development and implementation of COSs in dermatology. CS-COUSIN has developed guidance on how to develop high-quality COSs for skin diseases and supports dermatology-specific COS initiatives. Currently, 17 COS development groups are affiliated with CS-COUSIN and following standardized COS development processes. To ensure successful uptake of COSs in dermatology, researchers, clinicians, systematic reviewers, guideline developers, and other stakeholders should use existing COSs in their work., (Copyright © 2019 American Academy of Dermatology, Inc. All rights reserved.)

Background: Systemic autoinflammatory diseases (SAIDs) are rare debilitating disorders of which there is limited awareness and a significant delay in diagnosis. There is no uniform approach in the diagnosis and treatment of these disorders and the real life state of SAID patient care is poorly characterized. The aim of this study was to obtain data on the epidemiology, state of care and the perception of physicians who are involved in the care of SAID patients., Methods: We performed a questionnaire-based survey and contacted 134 university departments of dermatology, pediatrics, rheumatology and other SAID departments of tertiary care in German-speaking countries., Results: A total of 37 departments participated in the survey. The majority of departments managed both adult and pediatric patients with a variety of monogenic and polygenic/acquired SAIDs. For monogenic SAIDs such as cryopyrin-associated periodic syndromes (CAPS) and familial Mediterranean fever (FMF), the diagnostic and treatment strategies were similar among the departments. The diagnostic work-up included inflammatory markers and genetic testing, the first line treatment interleukin-1 (IL-1) blockers for CAPS and colchicine for FMF. For polygenic/acquired SAIDs, we observed a significant heterogeneity in diagnostic and therapeutic approaches. As a major unmet need, diagnostic delay was identified with a median time to diagnosis of 2 (range 1-5) years. The overall state of care for SAID patients was rated to be excellent or good by only 12% of departments, and to be poor or non-sufficient by 40% of departments., Conclusion: This study demonstrates a high need to improve the state of care and to harmonize diagnostic and treatment strategies for SAID patients.

Background: The urticaria control test (UCT) is a questionnaire designed to determine if chronic urticaria (CU) is controlled or not and to aid therapeutic decision-making. It collects retrospective information about the symptoms and quality of life impairment over the last 4 weeks. The current study aimed to investigate the validity, reliability and sensitivity to change of the Turkish version of the UCT. We also evaluated its correlation with other tools and compared the UCT results of patients with chronic spontaneous urticaria (CSU) and patients with chronic inducible urticaria (CINDU)., Methods: Following forward/backward translation and cognitive debriefing, the Turkish version of the UCT was used in 81 CSU and 78 CINDU patients. Dermatology life quality index (DLQI), Chronic urticaria quality of life questionnaire (CU-Q2oL), urticaria activity score (UAS), patients' and physicians' global assessment visual analog scores and Likert scales were used at baseline and after four weeks to assess quality of life impairment, disease activity and disease control. Statistical analysis to determine the validity and reliability of the Turkish version of the UCT as well as comparison between CINDU and CSU patients were performed., Results: Duration of disease was longer, disease control was poorer and severe complaints were more frequent in CINDU patients (duration of disease: 36.3 (24) ± 49.1 vs 31.5 (9) ± 67.9, p = .007, UCT baseline: 8.4 (8) ± 3.4 vs 10.4 (11) ± 3.9, p = .001 and patient's global assessment Likert scale severe complaints: 6 vs 15, p < .001, respectively). The UCT showed excellent internal consistency for CSU and a minimally acceptable consistency for CINDU ( Cronbach's α 0.89 for CSU versus 0.68 for CINDU). It showed strong correlation with CU-Q2oL but a moderate correlation with DLQI (r = -0.649, P < .001 and r = -0.545, P < .001, respectively). It was able to discriminate between patients with different disease control and was sensitive to detect changes in the disease control in both groups. The minimally important difference of the UCT was found to be 3., Conclusions: The Turkish version of the UCT is a valid and reliable tool for the management of CU patients and can be used both in CSU and CINDU patients to determine if the treatment is sufficient and if disease activity and quality of life impairment are under control or not.

Background: Data on the prevalence and disease management of chronic urticaria (CU) and chronic spontaneous urticaria (CSU) in the pediatric population are scarce. This study assessed the prevalence of CU and CSU, and disease management among pediatric patients (0-17 years)., Methods: A physician-based online survey was conducted in 5 European countries (United Kingdom, Germany, Italy, France, and Spain) assessing the annual diagnosed prevalence, disease characteristics, and treatment patterns in the target population. Results are based on physician responses and analyzed using descriptive statistics. Prevalence estimates were calculated based on the number of CU/CSU pediatric patients diagnosed, seen, and treated by the respondents and extrapolated to the total pediatric population from each country., Results: Across 5 European countries, the one-year diagnosed prevalence of CU and CSU in pediatric patients was 1.38% (95% CI, 0.94-1.86) and 0.75% (95% CI, 0.44-1.08), respectively. Angioedema was reported in 6%-14% of patients. A large proportion of CSU pediatric patients (40%-60%) were treated with H1-antihistamines at approved dose and 16%-51% received H1-antihistamines at higher doses. Approximately 1/3 of pediatric CSU patients remained uncontrolled with H1-antihistamines at approved/higher doses. Other prescribed treatments were oral corticosteroids (10%-28%) and topical creams (15%-26%)., Conclusions: This study revealed a prevalence of CSU among pediatric population comparable to adults and also suggested an unmet need for approved treatments for inadequately controlled pediatric CSU patients. It is truly of concern that harmful (oral steroids) or insufficient (topical creams) treatments were frequently used despite better and guideline-recommended alternatives., (© 2018 The Authors. Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd.)

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., (© 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Background: The approaches to the diagnosis and treatment of chronic spontaneous urticaria (CSU) differ in various parts of the world. We sought to determine the adherence to international and national urticaria guidelines as well as the motives to deviate from the guidelines among physicians worldwide., Methods: A web-based questionnaire was created and launched via e-mail by the World Allergy Organization (WAO) to representatives of all WAO Member Societies, the members of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the members of the WAO Junior Members Group (JMG), regardless of the specialty, affiliation, or nationality in March 2017., Results: We received 1140 completed surveys from participating physicians from 99 countries. Virtually all participants (96%) were aware of at least one urticaria guideline and reported that they follow a guideline. However, one in five physicians who follow a guideline (22%) reported to deviate from it. Reliance on own clinical experience is the most frequent reason for deviation from guidelines or not following them (44%). Young (< 40 years) and less experienced physicians more often follow a guideline and less often deviate than older and experienced ones. Physicians who follow a urticaria guideline showed higher rates of routinely ordering a complete blood count, the erythrocyte sedimentation rate, C-reactive protein, anti-thyroid antibodies, and thyroid-stimulating hormone and of performing the autologous serum skin test as compared to those who do not. Physicians who follow a urticaria guideline showed higher rates of using second generation antihistamines as their first-line treatment of CSU ( p  = 0.001) and more frequently observed higher efficacy of these drugs (or had more confidence that it would work, p  < 0.019) as compared to those who do not follow the guidelines., Conclusions: Physicians' characteristics (e.g. age, clinical experience, and specialty) and country specifics and regional features (e.g. availability of drugs for CSU treatment) importantly influence adherence to urticaria guidelines and CSU patient care and should be addressed in more detail in future research., Competing Interests: Not applicable.Not applicable.The authors declare they have no competing interests related to this work.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Chronic spontaneous urticaria is characterized by fluctuating symptoms. Its activity is assessed with the urticaria activity score (UAS). Two versions of the urticaria activity score used for 7 consecutive days (UAS7) are available: (1) The guideline-recommended UAS7, with once-daily documentation, and (2) the UAS7 TD , with twice-daily documentation., Objective: To better characterize both UAS7 versions with regard to their validity, reliability, sensitivity to change, minimal important difference (MID), and smallest detectable change (SDC)., Methods: One hundred thirty adult patients with chronic spontaneous urticaria completed both UAS7 versions, the Patients Global Assessment (PatGA) of disease activity, the Urticaria Control Test (UCT), the Chronic Urticaria Quality of Life Questionnaire, and the Dermatology Life Quality Index before and after the initiation of omalizumab therapy. Physicians completed a Physician Global Assessment of disease activity., Results: The UAS7 and the UAS7 TD showed high correlation with the activity anchor PatGA (r = 0.568, P < .001 and r = 0.605, P < .001) and the UCT (r = -0.580, P < .001 and r = -0.585, P < .001). The wheal and pruritus scores of the UAS7 and the UAS7 TD exhibited respectable internal consistency and, in each UAS7 version, correlated well with each other (Cronbach α = 0.78, r = 0.640, P < .001, and Cronbach α = 0.77, r = 0.626, P < .001). Changes in the UAS7 and UAS7 TD correlated well with PatGA changes (r = 639, P < .001, and r = .763, P < .001) and with UCT changes (r = -0.642, P < .001, and r = -0.703, P < .001). The MID was 11 for the UAS7 (SDC = 12) and 12 for the UAS7 TD (SDC = 11)., Conclusions: The UAS7 and UAS7 TD show good and comparable clinimetric properties, including good sensitivity to change, and similar MIDs., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The term prurigo has been used for many decades in dermatology without clear definition, and currently used terminology of prurigo is inconsistent and confusing. Especially, itch-related prurigo remains unexplored regarding the epidemiology, clinical profile, natural course, underlying causes, available treatments and economic burden, although burdensome and difficult to treat., Objective: To address these issues, the multicentre European Prurigo Project (EPP) was designed to increase knowledge on chronic prurigo (CPG). In the first step, European experts of the EADV Task Force Pruritus (TFP) aimed to achieve a consensus on the definition, classification and terminology of CPG. Additionally, procedures of the cross-sectional EPP were discussed and agreed upon., Methods: Discussions and surveys between members of the TFP served as basis for a consensus conference. Using the Delphi method, consensus was defined as an agreement ≥75% among the present members., Results: Twenty-four members of the TFP participated in the consensus conference. Experts consented that CPG should be used as an umbrella term for the range of clinical manifestations (e.g. papular, nodular, plaque or umbilicated types). CPG is considered a distinct disease defined by the presence of chronic pruritus for ≥6 weeks, history and/or signs of repeated scratching and multiple localized/generalized pruriginous skin lesions (whitish or pink papules, nodules and/or plaques). CPG occurs due to a neuronal sensitization to itch and the development of an itch-scratch cycle., Conclusion: This new definition and terminology of CPG should be implemented in dermatology to harmonize communication in the clinical routine, clinical trials and scientific literature. Acute/subacute forms of prurigo are separated entities, which need to be differentiated from CPG and will be discussed in a next step. In the near future, the cross-sectional EPP will provide relevant clinical data on various aspects of CPG leading to new directions in the scientific investigation of CGP., (© 2017 European Academy of Dermatology and Venereology.)

Objectives: To translate and linguistically validate the urticaria control test (UCT) to/for Arabic speakers. No Arabic version of the UCT is available to assess disease control in patients with chronic urticaria (CU). Secondary objectives were to assess disease control in Lebanese CU patients and determine influence factors., Methods: This is a prospective observational study of 178 CU patients diagnosed during their first visit to a private Allergy/Immunology Clinic, Hotel Dieu de France Hospital, Beirut, Lebanon between January and December 2014., Results: Factor analysis showed that all 4 UCT items on the Arabic version converged over a solution of one factor. A high internal consistency was found with a Cronbach's alpha of 0.824. Most patients in this study had chronic spontaneous urticaria (96%), of which 19% also had inducible urticaria. The majority was less than 40 years (67.4%), with disease duration of less than 2 years (70.8%). Most patients used H1-antihistamines, but unfortunately, 34.3% used systemic glucocorticosteroids, of which 24.7% also used H1-antihistamines. The disease was poorly controlled in most patients (79.2%, UCT less than 12). Age, gender, duration, diagnosis, triggers, and/or history of atopy had no influence., Conclusion: We developed the first linguistically validated Arabic UCT to improve CU management in Arabic speaking patients. We also found that disease control was poor in most CU patients, and is unaffected by age, disease duration, gender, subtype, triggers, history of atopy, and/or previous treatments.

Background and Objectives: "Off-label use" is defined as the prescription of pharmaceutical products outside their approved indications. Rare diseases frequently lack "on-label" treatment options. In order to avoid reimbursement claims following the prescription of off-label drugs, physicians in Germany can - on a case-by-case basis - file an application for cost coverage with the competent health insurance prior to treatment initiation., Patients and Methods: We conducted a chart review for cost coverage requests submitted by two outpatient clinics at a university-affiliated dermatology department between 2010 and 2012 (clinic for autoimmune diseases and urticaria clinic). Insurance providers, acceptance rates, reasons for rejection, and processing times were analyzed., Results: The analysis showed that 56.8 % of applications for off-label use (n = 44) were approved during the first round. The rate increased to 75.0 % when including approvals granted after up to two rejections. The time between initial application and the response of health insurers was 49 days (median). In case of cost coverage approval, treatments were initiated 92 days (median) after the initial request., Conclusions: The present case series shows that, in the majority of cases, health insurers in Germany have agreed to reimburse the costs of proposed off-label therapies. A prospective study is required in order to evaluate whether current changes to legal regulations (GKV-Versorgungsstrukturgesetz, Patientenrechtegesetz) adequately address the problems identified., (© 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Chronic spontaneous urticaria (CSU) is a mast cell-driven skin disease characterized by the recurrence of transient wheals, angioedema, or both for more than 6 weeks. Autoimmunity is thought to be one of the most frequent causes of CSU. Type I and II autoimmunity (ie, IgE to autoallergens and IgG autoantibodies to IgE or its receptor, respectively) have been implicated in the etiology and pathogenesis of CSU. We analyzed the relevant literature and assessed the existing evidence in support of a role for type I and II autoimmunity in CSU with the help of Hill's criteria of causality. For each of these criteria (ie, strength of association, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy), we categorized the strength of evidence as "insufficient," "low," "moderate," or "high" and then assigned levels of causality for type I and II autoimmunity in patients with CSU from level 1 (causal relationship) to level 5 (causality not likely). Based on the evidence in support of Hill's criteria, type I autoimmunity in patients with CSU has level 3 causality (causal relationship suggested), and type II autoimmunity has level 2 causality (causal relationship likely). There are still many aspects of the pathologic mechanisms of CSU that need to be resolved, but it is becoming clear that there are at least 2 distinct pathways, type I and type II autoimmunity, that contribute to the pathogenesis of this complex disease., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Schnitzler syndrome is an adult-onset autoinflammatory disease characterized by urticarial exanthema and monoclonal gammopathy accompanied by systemic symptoms such as fever, bone, and muscle pain. Up to now, approved treatment options are not available., Objective: We assessed effects of the anti-IL-1β mAb canakinumab on the clinical signs and symptoms of Schnitzler syndrome., Methods: In this phase II, randomized placebo-controlled multicenter study, 20 patients with active disease enrolled in 4 German study centers. Patients were randomly assigned to receive single subcutaneous canakinumab 150 mg or placebo injections for 7 days, followed by a 16-week open-label phase with canakinumab injections on confirmed relapse of symptoms. The primary end point was the proportion of patients with complete clinical response evaluated by physician global assessment at day 7. Key secondary end points included changes in patient-reported disease activity (Schnitzler activity score), inflammation markers (C-reactive protein and serum amyloid A), and quality-of-life assessments (Dermatology Life Quality Index and 36-item short form health survey)., Results: The proportion of patients with complete clinical response at day 7 was significantly higher (P = .001) in the canakinumab-treated group (n = 5 of 7) than in the placebo group (n = 0 of 13). Levels of inflammation markers C-reactive protein and serum amyloid A and quality-of-life scores were significantly reduced in canakinumab-treated but not in placebo-treated individuals. Positive effects continued up to 16 weeks. Adverse events were manageable and included respiratory tract infections, gastrointestinal symptoms, and hypertension., Conclusions: In this first placebo-controlled study, canakinumab was effective in patients with Schnitzler syndrome, and thus canakinumab may be further evaluated as a therapeutic option for this rare disease., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Psoriasis vulgaris is characterized by disfiguring and stigmatizing skin lesions. The links among lesions distribution, severity, and stigmatization remain unclear., Objective: We sought to investigate if the involvement of visible and sensitive areas is linked to stigmatization., Methods: In all, 115 patients with psoriasis vulgaris were assessed for disease severity, skin lesions distribution, itch, and stigmatization using the Feelings of Stigmatization Questionnaire. Quality of life was assessed with the Dermatology Life Quality Index and the World Health Organization Quality of Life-BREF., Results: The localization of psoriatic lesions on the back of hands was related to higher stigmatization levels (P = .011, total score of the Feelings of Stigmatization Questionnaire), but not the involvement of nails, the palms, the face, or the genital area nor overall disease severity. All patients reported some level of stigmatization, regardless of the localization of lesions and type of psoriasis. Higher levels of stigmatization characterized patients who claimed not to be able to hide their lesions by clothing (P = .025), women (P = .001), and the unemployed (P = .004). Stigmatization was the strongest predictor of quality of life impairment., Limitations: Only hospitalized patients were included., Conclusions: Psoriatic lesions on the back of hands are debilitating and warrant effective treatment. Special attention should be paid to female patients, who are more sensitive to stigmatization., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: To estimate health-related quality-of-life changes in patients with hereditary angioedema due to C1-inhibitor (C1-INH) deficiency who received subcutaneous C1-INH with recombinant hyaluronidase (rHuPH20) for attack prophylaxis in a randomized, double-blind, dose-ranging, cross-over study., Methods: Patients with type I/II hereditary angioedema received 1000 U of C1-INH with 24,000 U of rHuPH20 or 2000 U of C1-INH with 48,000 U of rHuPH20 every 3-4 days for 8 weeks and then crossed over for another 8-week period. The study was terminated early as a precaution related to non-neutralizing antibodies to rHuPH20. The Angioedema Quality of Life questionnaire (AE-QoL) was administered at weeks 1 and 5 of both periods, and at 1 week after the second treatment period. Changes in AE-QoL scores were calculated over both treatment periods and within each treatment period for patients with ≥4 weeks of treatment., Results: Forty-one patients had evaluable AE-QoL data, and 22 patients completed treatment. At screening, 43% of the patients were receiving intravenous C1-INH. A significant average AE-QoL total score decline (improvement) of -8.1 (95% confidence interval, -13.7 to -2.5) was observed from baseline to the end of the study, and significant AE-QoL score declines were observed in the Functioning, Fear/Shame, and Nutrition domains. Patients on 2000 U reported higher mean AE-QoL score declines in Functioning and Nutrition domains relative to the 1000 U dose. Overall, 43.9% of all the patients, 45.5% of the study completers, and 46.7% of the nonprophylaxis users at baseline on high treatment doses achieved a reduction in the AE-QoL total score of six points., Conclusion: Despite early termination and prestudy prophylactic intravenous C1-INH use by 43% of the patients, improved AE-QoL scores were observed after ≤16 weeks of subcutaneous C1-INH-rHuPH20 prophylaxis.

The use of standardized, valid, and reliable clinical measures is an important element in modern patient management, particularly in diseases that are not objectively assessable and are associated with a high disease burden. Chronic urticaria is such a disorder for which several new and well-developed clinical measures became available. These measures comprise tools to assess disease activity, disease control, and health-related quality-of-life impairment. This review provides an overview of the currently available clinical measures for chronic urticaria. In addition, it provides information on their strengths and limitations and how to best use them and evaluate their results., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The Angioedema Quality of Life Questionnaire (AE-QoL) has recently been developed and validated as the first specific patient-reported outcome tool to assess quality of life (QoL) impairment in recurrent angioedema patients. As of yet, its sensitivity to change and minimal clinically important difference (MCID) have not been established., Methods: Recurrent angioedema patients with chronic spontaneous urticaria or hereditary angioedema were repeatedly asked to complete the AE-QoL along with the SF-12 and other anchors for QoL impairment and disease activity during routine care visits. The sensitivity to change of AE-QoL was determined by correlating changes in its scores over time with changes in the applied anchors. In addition, the MCID was determined using anchor-based and distributional criterion-based approaches., Results: Two hundred and seventy-eight patients contributed data sets for analysis. Baseline AE-QoL values were found to correlate well with SF-12 results as well as all other applied anchors for angioedema-related QoL impairment and disease activity. In addition, AE-QoL score changes over time correlated significantly with changes in the above anchors, thus demonstrating its sensitivity to change. The MCID of the AE-QoL total score was found to be six points., Conclusion: The AE-QoL is a valuable tool to assess changes of QoL impairment in recurrent angioedema patients over time, including changes due to treatment., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The Long Form and Short Form of the German (original) version of the Urticaria Control Test (UCT) have shown to be valid and reliable instruments for assessing patients with all types of chronic urticaria (CU). The cutoff scores for identifying patients with well-controlled disease were  ≥  24 and  ≥  12 for Long and Short Forms, respectively. However, the sensitivity to change and minimal clinically important difference (MCID) of the UCT have never been systematically evaluated. This study aimed to investigate the validity, reliability, screening accuracy, sensitivity to change and MCID of the linguistically validated translation of the UCT into the Thai language for assessing CU in the Thai population., Methods: A structured translation and pre-testing were done to cross-culturally adapt the UCT for the Thai language. All measurement properties of both forms of the Thai UCT were validated in 169 patients with CU., Results: There were strong correlations between the Thai UCT score and disease activity, health-related quality of life impairment, and disease control (all correlations  ≥  0.7). Good internal consistency and excellent intra-rater reliability were demonstrated. The same cutoff scores to define patients with well-controlled disease should be used as those recommended for the original UCT version. MCIDs equated to increase in scores of 6 and 3 for the Long and Short Forms, respectively, of the Thai UCT should be used to identify patients who had minimal responses. Score increments of ≥ 10 and  ≥  6 for Long and Short Forms, respectively, should be used to define patients who had marked responses., Conclusions: This study confirmed the applicability of the UCT for use in Thailand, a country that has a very different language and cultural setting than that of Germany and the United States. Further studies are required to examine the suitability of the UCT for use in the pediatric population.

A major obstacle of evidence-based clinical decision making is the use of nonstandardized, partly untested outcome measurement instruments. Core Outcome Sets (COSs) are currently developed in different medical fields to standardize and improve the selection of outcomes and outcome measurement instruments in clinical trials, in order to pool results of trials or to allow indirect comparison between interventions. A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population. The international, multidisciplinary Cochrane Skin Group Core Outcome Set Initiative (CSG-COUSIN) aims to develop and implement COSs in dermatology, thus making trial evidence comparable and, herewith, more useful for clinical decision making. The inaugural meeting of CSG-COUSIN was held on 17-18 March 2015 in Dresden, Germany, as the exclusive theme of the Annual Cochrane Skin Group Meeting. In total, 29 individuals representing a broad mix of different stakeholder groups, professions, skills and perspectives attended. This report provides a description of existing COS initiatives in dermatology, highlights current methodological challenges in COS development, and presents the concept, aims and structure of CSG-COUSIN., (© 2016 British Association of Dermatologists.)

A 25-year-old woman presented to our clinic with a history of recurrent swelling and abdominal symptoms for > 20 years. The patient's father was similarly affected. The patient was diagnosed with hereditary angio-oedema (HAE) due to C1 inhibitor deficiency. This was initially managed with systemic androgens, but the symptoms of hyperandrogenism eventually became intolerable. Treatment with icatibant (an antagonist of bradykinin B2 receptors) was partially successful. We changed the therapy to prophylactic treatment with C1 inhibitor. Although the patient became completely symptom-free under this regimen, she found the repeated intravenous injections unacceptable. Therefore, we changed the route of administration to subcutaneous injections of C1 inhibitor 1000 U in 10 mL twice weekly, using a subcutaneous infusion kit. Since that time (December 2013), she has remained completely free of symptoms under this regimen. To our knowledge, this is the first report documenting the efficacy and safety of subcutaneous injections of C1 inhibitor in a patient with HAE., (© 2015 British Association of Dermatologists.)