Omalizumab rapidly improves angioedema-related quality of life in adult patients with chronic spontaneous urticaria: X-ACT study data

Background The X-ACT study aims to examine the effect of omalizumab treatment on quality of life (QoL) in chronic spontaneous urticaria (CSU) patients with angioedema refractory to high doses of H1-antihistamines. Methods In X-ACT, a phase III, double-blind, placebo-controlled study, CSU patients (18–75 years) with ≥4 angioedema episodes during the 6 months before inclusion were randomized (1:1) to receive omalizumab 300 mg or placebo every 4 weeks for 28 weeks. Angioedema-related QoL, skin-related QoL impairment, and psychological well-being were assessed. Results Ninety-one patients were randomized and 68 (omalizumab, n=35; placebo, n=33) completed the 28-week treatment period. At baselin…

Symptoms, course, and complications of abdominal attacks in hereditary angioedema due to C1 inhibitor deficiency.

Recurrent abdominal attacks belong to the cardinal and most distressing symptoms of hereditary angioedema (HAE) due to C1 inhibitor deficiency. They are characterized by crampy pain, but may include vomiting, diarrhea, and other features. Detailed clinical data about the symptoms and course of abdominal attacks have not been reported.We retrospectively observed a total of 33,671 abdominal attacks in 153 patients with HAE including a prospectively examined subgroup of 23 patients. Symptoms, course, frequency of attacks, and complications were analyzed.The relation of mild, moderate, and severe attacks was 1:1.4:5.6 in the prospective part of the study. Extra-abdominal symptoms preceded the a…

Efficacy of C1-Inhibitor Concentrate (Berinert®) for the Treatment of Cutaneous Attacks of Acute Hereditary Angioedema Compared to Historical Untreated Controls

Development and validation of the mastocytosis quality of life questionnaire: MC-QoL

Background Mastocytosis is a heterogeneous disease characterized by a clonal expansion of mast cells in various organs. The vast majority of patients affected suffer from signs and symptoms caused by mediator release from mast cells. Although the disease burden is high, there is currently no specific instrument to measure health-related quality of life (HRQoL) impairment in patients with mastocytosis. Objective The aim of this study was to develop and validate a disease-specific tool to assess HRQoL impairment in patients with cutaneous and indolent systemic mastocytosis, the Mastocytosis Quality of Life Questionnaire (MC-QoL). Methods Sixty-two potential MC-QoL items were developed in a co…

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria

Introduction: the COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. Aim: to understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19. Materials and methods: our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. Results: the COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers o…

Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial.

Current treatments for long-term prophylaxis in hereditary angioedema have limitations.To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks.Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary a…

Autologous whole blood injections to patients with chronic urticaria and a positive autologous serum skin test: a placebo-controlled trial.

<i>Background:</i> Patients with chronic urticaria (CU) frequently exhibit positive skin test reactions to autologous serum (ASST). Therapies aimed at inducing tolerance to circulating histamine-releasing factors in ASST+ CU patients, e.g. by treatment with autologous whole blood (AWB), have not yet been tested. <i>Objective:</i> To test whether ASST+ CU patients can benefit from repeated low-dose intramuscular injections of AWB. <i>Methods:</i> We characterized CU severity and duration, anti-Fc<sub>Ε</sub>RI and anti-IgE expression, use of antihistamines, and quality of life in 56 CU patients (ASST+: 35, ASST–: 21) and assessed the t…

Development and validation of the Urticaria Control Test: a patient-reported outcome instrument for assessing urticaria control.

Background Chronic urticaria is a frequent and debilitating skin disease. Its symptoms commonly fluctuate considerably from day to day. As of yet, the only reliable tool to assess disease activity is the Urticaria Activity Score, which prospectively documents the signs and symptoms of urticaria for several days. Objective We sought to develop and validate a novel patient-reported outcome instrument to retrospectively assess urticaria control, the Urticaria Control Test (UCT). Methods Potential UCT items were developed by using established methods (literature research and expert and patient involvement). Subsequently, item reduction was performed by using a combined approach, applying impact…

The EAACI/GA2LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update

This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioe…

Effect of single-dose and short-term administration of quercetin on the pharmacokinetics of talinolol in humans – Implications for the evaluation of transporter-mediated flavonoid–drug interactions

Quercetin has been shown to inhibit intestinal P-glycoprotein-mediated drug efflux. A crossover clinical study was performed in 10 healthy volunteers to assess the effect of single-dose and repeated quercetin intake on the pharmacokinetics of talinolol, a substrate of intestinal P-glycoprotein. Unexpectedly, mean area under the plasma concentration-time curve (AUC0-48h) and maximal plasma concentration (cmax) were slightly decreased following concomitant and short-term quercetin administration (3186.0 versus 2468.3 and 2527.7 ng h/ml, p>0.05; 309.7 versus 212.0 and 280.6 ng/ml, p>0.05). Individual analysis revealed that talinolol AUC0-48h was lowered by 23.9% up to 60.6% in 5 subjects and c…

Controversies and challenges in the management of chronic urticaria

This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. Despite the clear international guideline, there remain a number of controversies and challenges in the management of patients with chronic urticaria (CU). As a result of major advancements in urticaria over the past 4 years, the current EAACI/GA(2) LEN/EDF/WAO urticaria guideline treatment algorithm requires updating. Case studies from patients with chronic spontaneous urticaria (CSU) [also called chronic idiopathic urticaria (CIU)], chronic inducible urticaria (CIndU) or diseases and syndromes related to CU are useful in describing and exploring chall…

The global burden of chronic urticaria for the patient and society*

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 …

The Urticaria Activity Score-Validity, Reliability, and Responsiveness.

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 UAS7TD, 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 (PatG…

Diagnosis and treatment of xerosis cutis - a position paper.

Background and rationale Xerosis cutis (also referred to as xeroderma, dry skin, asteatosis) affects more than 10 million individuals in Germany. It is among the most common dermatological diagnoses and a cardinal symptom of many dermatological, internal and neurological diseases. Even though it has been established that basic skin care plays a significant role in the management of patients with xerosis cutis, there are as yet no evidence-based algorithms for diagnosis and treatment. Objective The present position paper provides physicians across all specialties with a practical, symptom-based approach to the prevention, diagnosis and treatment of xerosis cutis. Methods Within a structured …

IHAE-Qol: Specific Health-Related Quality Of Life (HRQoL) Questionnaire In Hereditary Angioedema Due To C1 Inhibitor Deficiency (HAE-C1INH)

Hereditary Angioedema Due to C1 Inhibitor Deficiency: New Findings Concerning Symptoms and Affected Organs

Maladaptive stress coping: An additional psychological factor in the process of chronification of pain or pruritus

Background: Inflammatory skin diseases with chronic pruritus and chronic back pain are very common symptoms in the general population and are associated with a reduced quality of life (QOL). In addition to biological factors, psychosocial reasons are also considered to be responsible for their development. So far, it is not known whether chronic pruritus and chronic back pain are related to maladaptive stress coping. Patients and methods: In our matched pilot case-control study with a total of 259 analyzed subjects, we compared outpatient groups, one suffering from chronic skin diseases with pruritus, the other with chronic back pain, to a healthy control group in terms of their stress copi…

Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase

Background A subgroup of patients with chronic spontaneous urticaria (CU) exhibits IgE antibodies directed against autoantigens, such as thyroperoxidase (TPO). We conducted this study to investigate whether such patients with CU with IgE against TPO benefit from treatment with omalizumab, a humanized anti-IgE mAb licensed for the treatment of severe persistent allergic (IgE-mediated) asthma. Objectives We sought to assess the efficacy of omalizumab treatment in patients with CU with IgE autoantibodies against TPO. Methods In this multicenter, randomized, double-blind, placebo-controlled study patients with CU (male/female, 18-70 years of age) with IgE autoantibodies against TPO who had pers…

Total IgE levels are linked to the response of chronic spontaneous urticaria patients to omalizumab

Epidemiology, comorbidities, and healthcare utilization of patients with chronic urticaria in Germany

Background. Comprehensive data on the epidemiology and comorbidities of chronic urticaria (CU) in Germany are either limited, or not contemporary. Objectives. To investigate the epidemiology of CU, overall comorbidities and healthcare resource utilized by patients with CU in Germany, using an anonymized statutory health insurance (SHI) database. Methods. Anonymized SHI claims research database of the Institute for Applied Health Research, Berlin [InGef] (01 January 2015-30 September 2018) was used to analyse insured individuals with a confirmed diagnosis of CU (ICD-10-GM codes). Twelve-month diagnosed prevalence and incidence, comorbidities (vs. atopic dermatitis and psoriasis), and healthc…

Grüntee‐Extrakt als erfolgreiche topische Behandlungsoption bei Kindern mit Condylomata acuminata im Perianalbereich

Positionspapier: Diagnostik und Therapie der Xerosis cutis.

Hintergrund und rationale Die Xerosis cutis (Synonym: Xerodermie, trockene Haut, hydrolipidarme Haut) ist mit > 10 Millionen Betroffenen nicht nur eine der haufigsten dermatologischen Diagnosen in Deutschland, sondern auch Leitsymptom vieler dermatologischer, internistischer und neurologischer Erkrankungen. Trotz der medizinischen Relevanz der topischen Basistherapie fur die Xerosis cutis gibt es in Deutschland fur ihr Management bisher keinen wissenschaftlich belegten Diagnostik- und Therapiealgorithmus. ZIEL: Dieses Positionspapier vermittelt Arzten fachubergreifend einen an individuellen Symptomen orientierten, praxisnahen Leitfaden fur die Pravention, Diagnostik und Therapie der Xerosis…

A Popular myth - low-histamine diet improves chronic spontaneous urticaria - fact or fiction?

Background Chronic spontaneous urticaria (CsU) is a frequent dermatological disease that might last for months or years with high impact on quality of life. Known causes are autoreactive phenomena, infections or intolerances, rarely IgE-mediated allergies. One third of CsU patients benefit from a low-pseudoallergen diet. Additionally, it is often discussed, that reducing histamine ingestion alone might improve clinical symptoms and quality of life in CsU-patients despite the uncertain role of the histamine-degrading enzyme diamine oxidase (DAO). Objective Aim of this study is to investigate the impact of low-histamine diet on symptoms and quality of life in patients with CsU. Methods Patien…

S2k guidelines for the treatment of psoriasis in children and adolescents - Short version part 1.

The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology, pediatrics, pediatric dermatology and pediatric rheumatology as well as policymakers and insurance funds. They were developed by dermatologists and pediatric dermatologists in collaboration with pediatric rheumatologists using a formal consensus process (S2k). The guidelines highlight topics such as disease severity, quality of life, treatment goals as well as problems associated with off-label drug therapy in children. Trigger factors and diagnostic aspects are discussed. The primary focus is on the various topical, systemic and UV-based treatment options available and includes recomm…

Extemporaneous formulations in Germany – relevance for everyday clinical practice

Background Extemporaneous formulations broaden the spectrum of therapeutic options for topical treatment in particular and thus improve patient care. The latest amendment to the Regulation on the Operation of Pharmacies issued in 2012 brought about changes in prescribing and manufacturing practices. The aim of the present study was to assess the relevance of extemporaneous formulations in everyday clinical practice. Methods We used data from the German Institute for Drug Use Evaluation (DAPI) to analyze the prescribing practice for compounded preparations in Germany between the fourth quarter of 2011 and the third quarter of 2014. In doing so, we determined the total cost associated with ex…

S2k guidelines for the treatment of psoriasis in children and adolescents - Short version part 2.

The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology, pediatrics, pediatric dermatology and pediatric rheumatology as well as policymakers and insurance funds. They were developed by dermatologists and pediatric dermatologists in collaboration with pediatric rheumatologists using a formal consensus process (S2k). The guidelines highlight topics such as disease severity, quality of life, treatment goals as well as problems associated with off-label drug therapy in children. Trigger factors and diagnostic aspects are discussed. The primary focus is on the various topical, systemic and UV-based treatment options available and includes recomm…

Methods report on the development of the 2013 revision and update of the EAACI/GA2 LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria

GA2LEN EAACI This methods report describes the process of guideline development in detail. It is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Th…

Validation of the Angioedema Control Test (AECT)—A Patient-Reported Outcome Instrument for Assessing Angioedema Control

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 o…

Green tea extract as a successful topical treatment option in children with perianal condylomata

A randomized trial of quilizumab in adults with refractory chronic spontaneous urticaria

Psychometric Field Study of Hereditary Angioedema Quality of Life Questionnaire for Adults:HAE-QoL

Background: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) may affect health-related quality of life (HRQoL). A specific HRQoL questionnaire for adult patients with C1-INH-HAE, the HAE-QoL, has recently been developed in Spain. Objective: The objective of this study was to perform a cross-cultural validation and psychometric study of the HAE-QoL in an international setting. Methods: Cross-cultural adaptation of the Spanish HAE-QoL draft version and an international rating phase with experts were performed. The resultant version of the HAE-QoL, a clinical questionnaire, and Short Form 36-item Health Survey Version 2.0 (SF-36v2) were pilot tested internationally. Item reduc…

Sustained safety and efficacy of ligelizumab in patients with chronic spontaneous urticaria: A one‐year extension study

Background: Ligelizumab, a next-generation, humanized anti-immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms are inadequately controlled with standard-of-care therapy. Objective: To evaluate the long-term safety and re-treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study. Methods: This open-label, single-arm, long-term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose-finding core study and who presented with active disease after Week 32. In …

Development and construct validation of the angioedema quality of life questionnaire

Background Recurrent angioedema is a frequent clinical problem characterized by unpredictably and rapidly occurring cutaneous and mucosal swellings. These swellings may be painful and/or disfiguring. Upper airway involvement can also lead to dyspnea and suffocation. Although the disease burden is high, there is currently no specific instrument to measure health-related quality of life (QoL) impairment. Objective To develop and validate the first symptom-specific tool to assess QoL impairment in recurrent angioedema patients, adhering to established methodological recommendations. Methods During the development phase, 29 questions (items) were generated. Subsequently, item reduction was perf…

Allergen-Immuntherapie in der aktuellen COVID-19-Pandemie – ein Positionspapier von ARIA, EAACI, AeDA, GPA und DGAKI (Kurzversion) – Positionspapier der deutschen ARIA-GruppeA in Kooperation mit der österreichischen ARIA-GruppeB, der schweizerischen ARIA-GruppeC, dem Ärzteverband Deutscher Allergologen (AeDA)D, der Deutschen Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)E und der Gesellschaft für Pädiatrische Allergologie (GPA)F in Kooperation mit der AG Klinische Immunologie, Allergologie und Umweltmedizin der DGHNO-KHCG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H

High-Concentration Liquid Prednisolone Formula: Filling a Therapeutic Niche in Severe Acute Attacks of Urticaria and Angioedema.

<b><i>Background/Aims:</i></b> According to current guidelines, the emergency kit for patients with severe urticaria and/or angioedema should include a corticosteroid with a prednisolone-equivalent of 50-100 mg. Since severe dysphagia may occur in anaphylaxis, liquid corticosteroids are advantageous. Presently, only liquid preparations with less than 100 mg prednisolone equivalent are available worldwide. <b><i>Methods:</i></b> We prepared a highly concentrated liquid prednisolone formula for oral administration (1 or 5 mg prednisolone per ml). We observed efficacy and safety of 100 mg or >250 mg liquid oral prednisolone in comparison to in…

Severe chronic spontaneous urticaria in children – treatment options according to the guidelines and beyond – a 10 years review

This is a retrospective study of 18 children with chronic spontaneous urticaria (CSU), where standard therapies, including up-dosing of antihistamines and omalizumab, were unable to cure the disease and where alternative strategies with experimental and off-label medication had to be used. Being aware that our questionnaire is validated only for elder children or adults, we utilized the UAS7 to monitor disease control with the help of the parents. The UAS7 score decreased from a mean of 25 to an average of 13 after 8 weeks of therapy in 13 patients. Five patients had no significant reduction of UAS7 by week 8. In two of five patients, where periodic improvement was seen, omalizumab therapy …

Effect of high-dose intravenous immunoglobulin treatment in therapy-resistant chronic spontaneous urticaria

Background Chronic spontaneous urticaria (CSU) lasting more than 6 weeks is one of the most disabling types of urticaria and often results in severely impaired quality of life. Patients with CSU are often unsatisfied with the standard treatment. Another treatment option recommended for patients with so-called nonresponding CSU according to the newest guidelines is intravenous immunoglobulin (IVIG). Objective To assess the efficacy and safety of high-dose IVIG as a treatment option in patients with therapy-resistant CSU. Methods Six patients with severe CSU unresponsive to other treatment options according to the newest guidelines for several weeks were treated with high-dose IVIG (2 g/kg ev…

A randomized, multinational, noninferiority, phase III trial to evaluate the safety and efficacy of BF-200 aminolaevulinic acid gel vs. methyl aminolaevulinate cream in the treatment of nonaggressive basal cell carcinoma with photodynamic therapy

Background: Basal cell carcinoma (BCC) represents the most common nonmelanoma skin cancer worldwide, affecting mainly adult, fair-skinned individuals. The World Health Organization distinguishes aggressive and nonaggressive forms, of which prototypical variants of the latter are primary nodular and superficial BCC. Objective: To demonstrate noninferiority of BF-200 ALA (a nanoemulsion gel containing 5-aminolaevulinic acid) compared with MAL (a cream containing methyl aminolaevulinate) in the treatment of nonaggressive BCC with photodynamic therapy (PDT). Noninferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean …

Urticaria in Pediatrics and During Pregnancy and Lactation: Highlights on Epidemiology, Diagnosis, and Management

Chronic urticaria (CU) in children as in adults is characterized by the presence of itchy wheals, angioedema, or both daily or almost daily for at least 6 weeks. Most cases of urticaria in the pediatric age group are acute [1–4]. CU is sub-classified as spontaneous (occurring without a known trigger) or inducible. There are also cases of spontaneous and inducible forms that co-exist. The chronic subtypes occur continuously but also recurrently, often in association with infections. In this chapter we will touch briefly on the clinical presentation, diagnosis, and management of acute urticaria in children. However, our primary goal is to highlight key findings regarding the epidemiology, dia…

A European survey of management approaches in chronic urticaria in children: EAACI Paediatric Urticaria Taskforce

Background: Although well described in adults, there are scarce and heterogeneous data on the diagnosis and management of chronic urticaria (CU) in children (0-18 years) throughout Europe. Our aim was to explore country differences and identify the extent to which the EAACI/GA²LEN/EDF/WAO guideline recommendations for paediatric urticaria are implemented. Methods: The EAACI Taskforce for paediatric CU disseminated an online clinical survey among EAACI paediatric section members. Members were asked to answer 35 multiple choice questions on current practices in their respective centres. Results: The survey was sent to 2,773 physicians of whom 358 (13.8%) responded, mainly paediatric allergist…

Epidemiology of urticaria in German children

Background To date, robust epidemiological metrics as well as data on comorbidity in pediatric urticaria are lacking. They form the basis for the design of efficient healthcare. Methods Retrospective study to analyze epidemiological data in pediatric urticaria. The analysis is based on routine data of a health insurance company operating throughout Germany (DAK-Gesundheit). Insured people under 18 years of age who received at least one confirmed outpatient or inpatient urticaria diagnosis according to the ICD-10 classification in the years 2010 to 2015 were included in the analysis and compared to children without a corresponding diagnosis. Results Of 2.3 million insured individuals, 313,58…

High prevalence and little awareness in patients with chronic inflammatory skin diseases and genital involvement.

Background Genital involvement in patients with chronic inflammatory skin diseases is frequent, yet insufficiently acknowledged. Objective To evaluate the prevalence of genital symptoms in psoriasis and chronic urticaria patients, effects on quality of life, physician-patient relations and disease management. Patients and methods 100 patients with psoriasis and 100 with chronic urticaria from our outpatient clinic, as well as 50 healthy controls were included. Data was collected using questionnaires developed by dermatological experts. Results Out of 250 subjects, 74 % had already experienced genital symptoms - 70 % of psoriasis patients and 58 % of urticaria patients. Seven out of ten even…

S2k-Leitlinie zur Diagnostik und Therapie des chronischen Pruritus - Update - Kurzversion

Development of the Angioedema Control Test—A patient‐reported outcome measure that assesses disease control in patients with recurrent angioedema

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-it…

EAACI/GA²LEN/EDF/WAO guideline: management of urticaria

This guideline, together with its sister guideline on the classification of urticaria (Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Gimenez-Arnau AM et al. EAACI/GA(2)LEN/EDF/WAO Guideline: definition, classification and diagnosis of urticaria. Allergy 2009;64: 1417-1426), is the result of a consensus reached during a panel discussion at the Third International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF) and the World Al…

Dermatologische Rezepturen in Deutschland - Relevanz für die Versorgung.

Omalizumab is effective in symptomatic dermographism-results of a randomized placebo-controlled trial.

Peltier effect-based temperature challenge: an improved method for diagnosing cold urticaria.

Health-Related Quality Of Life (HRQoL) In Adult Patients With Hereditary Angioedema Due To C1 Inhibitor Deficiency (HAE-C1-INH) Assessed By SF-36v2

Compounded preparations in dermatology – analysis of prescribing habits in everyday clinical practice in Germany

Background Compounded preparations (CPs) are an indispensable addition to approved, commercially available drugs (CADs), especially for topical therapy. In Germany, about eight million CPs are prescribed within the statutory health insurance system each year, 50 % thereof by dermatologists. Methods We analyzed prescribing habits based on a questionnaire sent out to 186 office-based dermatologists and 1,491 pharmacies in the federal states of Rhineland-Palatinate and Saarland. The goal was to improve patient care by collecting and categorizing data in terms of prescription practice and associated challenges in interdisciplinary cooperation. Results Overall, 351 pharmacists (23.5 %) and 53 de…

Effect of omalizumab on angioedema in H1-antihistamine-resistant chronic spontaneous urticaria patients: results from X-ACT, a randomized controlled trial

Background Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied. Objective The primary objective was to evaluate the efficacy of omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives. Methods X-ACT was a phase III, rand…

ATTENTUS, a German online survey of patients with chronic urticaria highlighting the burden of disease, unmet needs and real-life clinical practice.

Antihistamine-resistant chronic spontaneous urticaria: 1-year data from the AWARE study.

BACKGROUND Previous reports indicate that patients with chronic spontaneous urticaria (CSU) are undertreated and that physicians show poor adherence to guideline recommendations. Awareness of CSU has improved in recent years, but it remains unclear if this has improved the management of these patients in clinical practice. OBJECTIVE To describe disease burden, quality of life (QoL), and treatment patterns of patients with H1 -antihistamine-refractory CSU in Germany. METHOD A World-wide Antihistamine-Refractory chronic urticaria (CU) patient Evaluation (AWARE) is a global prospective, non-interventional study of CU in the real-world setting, supported by the manufacturer of omalizumab. Patie…

High Prevalence of Mental Disorders and Emotional Distress in Patients with Chronic Spontaneous Urticaria

Quality of life, which is impaired in patients with chronic spontaneous urticaria (CSU), is influenced by comorbid mental disorders. The aim of this study was to assess the prevalence and spectrum of mental disorders and to determine levels of emotional distress in patients with CSU. One hundred patients with CSU were investigated for mental disorders (by specialized diagnostic interviews and psychometric instruments), levels of emotional distress (by the Global Severity Index of the Symptom Check List; SCL-90R GSI) and underlying causes of their urticaria (by dermatological assessment). Forty-eight percent of patients with CSU were diagnosed with one or more psychosomatic disorders; most c…

LAight® Therapy Significantly Enhances Treatment Efficacy of 16 Weeks of Topical Clindamycin Solution in Hurley I and II Hidradenitis Suppurativa: Results from Period A of RELIEVE, a Multicenter Randomized, Controlled Trial.

<b><i>Background:</i></b> Hidradenitis suppurativa (HS) is a chronic, inflammatory, burdensome skin disease where medical first-line treatment is still limited to long-term, topical and/or systemic antibiotics. The RELIEVE study aimed at evaluating the efficacy of LAight® therapy – a combination of intense pulsed light and radiofrequency – as an adjunct treatment to first-line therapies in Hurley stage I and II HS. <b><i>Methods:</i></b> The RELIEVE study was performed as a two-period multicenter randomized controlled trial with blinded assessment. For period A from week 0 to week 16, the 88 participating subjects were randomized into either a…

Treatment With Pasteurized C1 Inhibitor Concentrate In Skin Swelling Attacks Of Patients With Hereditary Angioedema

S2k guidelines for the use of topical preparations on the skin

The present guidelines are aimed at dermatology residents and board-certified dermatologists as well as policymakers and insurance companies. Developed by dermatologists in collaboration with pharmacists using a formal consensus process (S2k), they include general aspects with respect to pharmacokinetics and regulatory terminology. Recommendations are provided on the various indications for extemporaneous preparations and their quality assurance. The importance of pharmaceutical vehicles and problems associated with substituting one vehicle for another are discussed. The guidelines include criteria for choosing a suitable pharmaceutical vehicle and for specific aspects in terms of treatment…

Development, validation, and initial results of the Angioedema Activity Score

Background Recurrent angioedema (RecA) is a frequent clinical problem characterized by suddenly occurring cutaneous and/or mucosal swellings. Depending on their location, RecA may be painful, hindering, disfiguring, or even life-threatening. The assessment of disease activity in affected patients is important to guide treatment decisions. Currently, however, there is no standardized and validated outcome measure available to do so. Objective To develop and validate the first specific patient-reported outcome instrument to assess disease activity in RecA patients, the Angioedema Activity Score (AAS). Methods After a set of potential AAS items was developed, item evaluation and reduction were…

Treatment with C1 inhibitor concentrate in abdominal pain attacks of patients with hereditary angioedema

BACKGROUND: Abdominal edema attacks in patients with hereditary angioedema are often extremely painful, associated with vomiting and diarrhea, and have a high potential for causing recurrent disability of the patient. STUDY DESIGN AND METHODS: Intraindividual comparison of retrospective data in 75 hereditary angioedema patients comprising 4,834 abdominal attacks treated with C1 inhibitor concentrate versus 17,444 untreated abdominal attacks. RESULTS: The mean duration of abdominal attacks was 92.0 hours (SD, 40.8 hr) when untreated compared to 39.9 hours (SD, 30.0 hr) when treated. Patients reported a mean maximal pain score of 8.6 (SD, 1.7; range, 1-10) for untreated attacks compared to 4.…

Efficacy of C1 esterase inhibitor concentrate in treatment of cutaneous attacks of hereditary angioedema.

BACKGROUND Although treatment with C1 esterase inhibitor (C1-INH) concentrate is well established for hereditary angioedema (HAE) attacks in general, data that assess its efficacy for cutaneous attack treatment are sparse. OBJECTIVE To assess efficacy of plasma-derived, nanofiltered C1-INH concentrate for cutaneous attack treatment by comparing treated attacks from the uncontrolled I.M.P.A.C.T.2 study with historical data for untreated attacks. METHODS Cutaneous attack data from patients with HAE who were treated for cutaneous edema with 20 IU/kg body weight C1-INH concentrate in the uncontrolled I.M.P.A.C.T.2 study (38 patients) were compared with data from untreated patients from an histo…

Omalizumab is effective in cold urticaria—results of a randomized placebo-controlled trial

Definition, aims, and implementation of GA [sup] 2 LEN/HAEi Angioedema Centers of Reference and Excellence

This document summarizes the aims of GA2 LEN/HAEi Angioedema Centers of Reference and Excellence (ACAREs) and elaborates the requirements that ACAREs must fulfill to become certified. It also provides (see Appendix S1) background information on GA2LEN and HAEi, including HAEi member organizations and regional patient advocates, on why we need an Angioedema Center of Reference and Excellence (ACARE) program and network, and on the accreditation and certification process, governance and funding, and on the interaction with other GA2LEN networks of centers of reference and excellence. The protocols, aims, requirements, and provisions related to becoming a certified CARE are based on (a) the ex…

The Influence of Chitosan on the Oral Bioavailability of Acyclovir-a Comparative Bioavailability Study in Humans

Purpose The effects of chitosan hydrochloride on the oral absorption of acyclovir in humans were studied to confirm the absorption enhancing effects reported for in vitro and rat studies, respectively. Methods A controlled, open-label, randomized, 3-phase study was conducted in 12 healthy human volunteers. Zovirax 200 mg dispersible tablets co-administered with doses of 400 and 1000 mg chitosan HCl were compared with Zovirax only. Results The expected increased absorption of acyclovir was not observed. On the contrary, mean area under the plasma concentration-time curve (AUC0-12 h) and maximal plasma concentration (Cmax) decreased following concomitant chitosan intake (1402 versus 1017 and …

S2k-Leitlinie zum Gebrauch von Präparationen zur lokalen Anwendung auf der Haut (Topika)

Diese Leitlinie richtet sich an Assistenz- und Facharzte der Dermatologie sowie an Kostentrager und politische Entscheidungsgremien. Die Leitlinie wurde im formellen Konsensusverfahren (S2k) von Dermatologen unter Einbindung von Apothekern erstellt. Die Leitlinie stellt allgemeine Aspekte der Pharmakokinetik sowie der regulatorischen Begrifflichkeiten dar. Es werden Empfehlungen zur Indikation von Magistralrezepturen sowie deren Qualitatssicherung gegeben. Die Bedeutung der galenischen Grundlagen und die Problematik bei einer Substitution gegeneinander verschiedener Grundlagen werden dargestellt. Die Leitlinie umfasst Kriterien zur Auswahl einer adaquaten Grundlage sowie spezifische Aspekte…

Intravenous Immunoglobulin as a Third-Line Therapy in Chronic Spontaneous Urticaria

Mastocytosis - pathogenesis, clinical manifestation and treatment

The term mastocytosis designates a group of rare disorders characterized by typical skin lesions, frequently associated episodes of anaphylaxis, and clinical symptoms related to the release of various mediators. Dermatologists/allergists are frequently the first to establish the diagnosis. The condition is based on clonal mast cell proliferation, usually in the skin or bone marrow and only rarely in the gastrointestinal tract or other tissues. In general, mastocytosis has a good prognosis in terms of life expectancy. Rare variants - including mast cell leukemia, aggressive mastocytosis, and the exceedingly rare mast cell sarcoma - require cytoreductive therapy. In cases associated with hema…

Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy.

Background Hereditary angioedema caused by mutations in the factor XII gene is a recently described disease entity that occurs mainly in women. It differs from hereditary angioedema caused by C1 inhibitor deficiency. Objective To assess the clinical symptoms, factors triggering acute attacks, and treatments of this disease. Methods Thirty-five female patients with hereditary angioedema and the factor XII mutations p.Thr309Lys and p.Thr309Arg who came from 13 unrelated families were studied. The observation period was 8.4 years on average (range, 2-26 years). Results Patients had on average 12.7 ± 7.9 angioedema attacks per year. Recurrent facial swellings occurred in all patients; skin swel…

Comparison and interpretability of the available urticaria activity scores

The urticaria activity score (UAS) is the gold standard for assessing disease activity in patients with chronic spontaneous urticaria (CSU). Two different versions, the UAS7 and UAS7TD , are currently used in clinical trials and routine care. To compare both versions and to obtain data on their interpretability, 130 CSU patients applied both versions and globally rated their disease activity as none, mild, moderate, or severe. UAS7 and UAS7TD values correlated strongly (r = .90, P < .001). Interquartile ranges for UAS7 and UAS7TD values for mild, moderate, and severe CSU were 11-20 and 10-24, 16-30 and 16-32, and 27-37 and 28-40. UAS7 values were slightly, but significantly lower as compare…

Effects of topical treatment with the raft modulator miltefosine and clobetasol in cutaneous mastocytosis: a randomized, double-blind, placebo-controlled trial

Background Mastocytosis is characterized by the accumulation and activation of mast cells in different organs, most commonly the skin. Miltefosine, a raft modulator, has recently been shown to inhibit the activation of mast cells and to reduce mast cell-driven skin inflammatory responses. Objectives To study the safety and efficacy of topical miltefosine treatment of skin lesions in patients with mastocytosis. Methods Thirty-nine adult patients with mastocytosis with skin involvement were treated in a double-blind, placebo-controlled, parallel trial with topical miltefosine and clobetasol for 2 weeks. Treatment areas were analysed for changes in skin lesions and symptoms following mechanica…

C1 Inhibitor for Routine Prophylaxis in Patients with Hereditary Angioedema: Interim Results from a European Registry Study

The Angioedema Quality of Life Questionnaire (AE-QoL) - assessment of sensitivity to change and minimal clinically important difference

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 …

Hereditary Angioedema: New Findings Concerning Symptoms, Affected Organs, and Course

Abstract Purpose Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Our aim was to examine a temporal and spatial pattern of the edema episodes by evaluating the long-term course of hereditary angioedema in order to establish a specific swelling pattern. Subjects and methods Data were generated from 221 patients with C1 inhibitor deficiency by asking them about symptoms they experienced during their edema episodes. Documentation was accomplished through the use of standardized questionnaires. Results A total of 131110 edema episodes were observed. Clinical …

The Influence of Single-Dose and Short-Term Administration of Quercetin on the Pharmacokinetics of Midazolam in Humans.

Quercetin is a plant flavonol that is available from both daily diet and nutraceuticals. To investigate the effect of acute and short-term intake of high-dose quercetin on CYP3A-mediated metabolism, 10 healthy volunteers received 7.5 mg oral midazolam without, with a single dose of 1500 mg quercetin and after 1-week supplementation with 1500 mg quercetin daily. A substudy was performed in three subjects to explore the impact of repeated quercetin intake on intravenously administered midazolam. Coadministration with a single dose of quercetin did not significantly alter the pharmacokinetics of midazolam and its 1'-hydroxymetabolite, but following short-term quercetin intake, there was a tren…

Substance P is upregulated in the serum of patients with chronic spontaneous urticaria.

Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy

Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H1-antihistamines along with 1 or more add-on therapies.We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H₁-antihistamines at up to 4 times the approved dose plus H₂-antihistamines, leukotriene receptor antagonists, or both.In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period. The primary object…

Responsiveness and minimal important difference of the urticaria control test

This study demonstrates the responsiveness of the Urticaria Control Test (UCT). Changes of its score by 3 points or more reflect a clinically relevant change of disease control (minimal important difference).

Quality of life in patients with chronic urticaria is differentially impaired and determined by psychiatric comorbidity

Summary Background  Chronic urticaria (CU), one of the most common skin disorders, is characterized by spontaneous recurrent bouts of weals and pruritus and associated with severely impaired quality of life (QoL). Objectives  To determine what aspects of life quality are affected and to characterize the factors that impact on QoL in CU patients. Subjects and methods  This interdisciplinary interview/questionnaire-based study included 100 patients admitted to a University Hospital Dermatology Department for the identification of underlying causes of CU; 96 healthy subjects matched for age and sex were used as controls. QoL was assessed using Skindex-29, a validated instrument to measure the …

Treatment of skin swellings with C1-inhibitor concentrate in patients with hereditary angio-oedema.

Background:  Skin swellings are the most frequent symptoms in hereditary angio-oedema (HAE) arising out of C1-inhibitor (C1-INH) deficiency. They may be painful and impact daily activities of patients. Detailed clinical data concerning the treatment of skin swellings by C1-INH concentrate have not been reported yet. Methods:  From 1976 through 2007, a total of 2104 skin-swelling attacks in 47 patients with HAE were treated with the C1-INH concentrate. Time to relief and duration of the swellings were documented during personal interviews using standardized questionnaires. The results were compared with 9046 untreated skin swellings in the same patients. Results:  The first clinical sign of …

Urticaria in children and adolescents: An updated review of the pathogenesis and management

The present survey represents the latest data on diagnosis and management of childhood urticaria. It has been observed that urticaria occurs less often in children than adults, with symptoms rarely lasting for over 6 weeks. Triggers or aggravating factors can be found only in 21%-55% of cases. Finding autoantibodies in children does not impact a disease prognosis, unlike in adult patients, where the presence of autoantibodies is associated with a more prolonged run of the disease, a more severe prognosis and more intensive treatment methods. The incidence of food allergy equals to 8%-10% of cases. The incidence of Helicobacter Pylori infection in children is lower than that in adults and co…

Wytyczne EAACI/GA2LEN/EDF/WAO dotyczące definicji, klasyfikacji, rozpoznawania i leczenia pokrzywki: weryfikacja z 2013 roku z poprawkami

Streszczenie Niniejsze wytyczne są wynikiem systematycznego przeglądu piśmiennictwa dokonanego w oparciu o metodologie GRADE ( Grading Recommendations Assessment, Development and Evaluation ) oraz dyskusji przeprowadzonych w trakcie konferencji dotyczącej pokrzywki, ktora odbyla sie 28 i 29 listopada 2012 roku w Berlinie. Konferencja ta byla wspolną inicjatywą kilku organizacji ( Dermatology Section of the European Academy of Allergy and Clinical Immunology [EAACI], EU-funded network of excellence, Global Allergy and Asthma European Network [GA 2 LEN], European Dermatology Forum [EDF], World Allergy Organization [WAO]) i wzieli w niej udzial delegaci z 21 towarzystw zarowno krajowych, jak i…

Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study.

Background: Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high-affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU. Methods: This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti-FcεRI and IgG anti-IgE; IgG-anti-thyrop…

High-dose short-term administration of naringin did not alter talinolol pharmacokinetics in humans.

Naringin is considered the major causative ingredient of the inhibition of intestinal drug uptake by grapefruit juice. Moreover, it is contained in highly dosed nutraceuticals available on the market. A controlled, open, randomized, crossover study was performed in 10 healthy volunteers to investigate the effect of high-dose naringin on the bioavailability of talinolol, a substrate of intestinal organic anion-transporting polypeptide (OATP)-mediated uptake. Following 6-day supplementation with 3 capsules of 350 mg naringin daily, 100mg talinolol were administered orally with 3 capsules of the same dietary supplement (1050 mg naringin) on the seventh day. This test treatment was compared to …