Consensus on the Definition of Control and Remission in Chronic Urticaria.

The terms control and remission and other key terms used in chronic urticaria (CU) such as flare-up, relapse, exacerbation, and recurrence have not been fully defined in the literature. Disease monitoring and treatment goals in clinical practice are not well established. After a qualitative appraisal of available evidence, we aimed to find a consensus definition of control and remission, clarify key terminology, provide guidance on how to monitor the disease, and establish treatment goals in clinical practice. A modified Delphi consensus approach was used. Based on a literature review, a scientific committee provided 137 statements addressing controversial definitions and terms, available patient-reported outcomes (PROs), and recommendations on how to measure therapeutic objectives in CU. The questionnaire was evaluated by 138 expert allergists and dermatologists. A consensus was reached on 105 out of the 137 proposed items (76.6%). The experts agreed that complete control and remission of CU could be defined as the absence of signs or symptoms while on treatment and in the absence of treatment, respectively. Consensus was not reached on the definition of other key terms such as flare-up, exacerbation, and recurrence. The panel agreed that the objective of therapy in CU should be to achieve complete control. PROs that define the degree of control (complete, good, partial, or absence) were established. An algorithm for disease assessment is provided. In conclusion, this work offers consensus definitions and tools that may be useful in the management of patients with CU.

A Specialized Therapeutic Approach to Chronic Urticaria Refractory to H1-Antihistamines Improves Disease Burden: The Spanish AWARE Experience.

OBJECTIVE: During its first year, the AWARE study assessed disease activity, patient quality of life (QOL), and treatment patterns in chronic urticaria (CU) refractory to H1-antihistamines (H1-AH) in clinical practice. METHODS: We performed an observational, prospective (24 months), international, multicenter study. The inclusion criteria were age ≥18 years and H1-AH-refractory CU (>2 months). At each visit, patients completed questionnaires to assess disease burden (Urticaria Control Test [UCT]), disease activity (7 day-Urticaria Activity Score [UAS7]), and QOL (Dermatology Life Quality index [DLQI], Chronic Urticaria Quality of Life Questionnaire [CU-Q2oL], and Angioedema Quality of Life Questionnaire [AE-QoL]). We present data for Spain. RESULTS: The study population comprised 270 evaluable patients (73.3% female, mean [SD] age, 48.9 [14.7] years). At baseline, 89.3% were prescribed a CU treatment. After 1 year, first- and second-line treatments became less frequent and third-line treatments became more frequent. At baseline, 47.0% of patients experienced angioedema; at 1 year, this percentage had fallen to 11.8%. The mean (SD) AE-QoL score decreased from 45.2 (28.7) to 24.0 (25.8). The mean (SD) UCT score decreased from 7.0 (4.5) to 12.1 (4.1). According to UAS7, 38.2% of patients reported absence of wheals and itch in the previous 7 days at 1 year compared with 8.3% at baseline. The mean (SD) DLQI score decreased from 8.0 (7.4) to 2.8 (4.6). At the 1-year visit, the percentage of patients reporting a high or very high impact on QOL fell from 29.9% to 9.6%. CONCLUSION: H1-AH-refractory CU in Spain is characterized by absence of control of symptoms and a considerable impact on QOL. Continuous follow-up of CU patients and third-line therapies reduce disease burden and improve patients' QOL.

Changing perspectives in atopic dermatitis.

Atopic dermatitis (AD) is a multifaceted disease that involves a complex interplay between the skin and the immune system. The course of the disease depends strongly on the genetic background of the patient and on yet poorly-defined environmental factors. Changes in lifestyle could be behind the dramatic rise in the prevalence of AD across continents; including hygienic conditions, food, social habits, skin microbiome or exposure to a number of allergens. Although AD typically develops in childhood and disappears after a few years, in a relatively large number of patients it continues into adulthood. Adult AD can also appear de novo but it is often underdiagnosed and its treatment can be challenging. New, highly effective drugs are being developed to manage moderate and severe forms of the disease in adults. In this review, we highlight the most recent developments in diagnostic tools, current insights into the mechanistic basis of this disease, and therapeutic innovations.

Management of chronic spontaneous urticaria in routine clinical practice: A Delphi-method questionnaire among specialists to test agreement with current European guidelines statements.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a frequent clinical entity that often presents a diagnostic and therapeutic challenge. OBJECTIVE: To explore the degree of agreement that exists among the experts caring for patients with CSU diagnosis, evaluation, and management. METHODS: An online survey was conducted to explore the opinions of experts in CSU, address controversial issues, and provide recommendations regarding its definition, natural history, diagnosis, and treatment. A modified Delphi method was used for the consensus. RESULTS: The questionnaire was answered by 68 experts (dermatologists, allergologists, and primary care physicians). A consensus was reached on 54 of the 65 items posed (96.4%). The experts concluded that CSU is a difficult-to-control disease of unpredictable evolution. Diagnostic tests should be limited and based on clinical history and should not be indiscriminate. Autoinflammatory syndromes and urticarial vasculitis must be ruled out in the differential diagnosis. A cutaneous biopsy is only recommended when wheals last more than 24h, to rule out urticarial vasculitis. The use of specific scales to assess the severity of the disease and the quality of life is recommended. In patients with severe and resistant CSU, second-generation H1-antihistamines could be used at doses up to four times the standard dose before giving second-line treatments. Omalizumab is a safe and effective treatment for CSU that is refractory to H1-antihistamines treatment. In general, diagnosis and treatment recommendations given for adults could be extrapolated to children. CONCLUSIONS: This work offers consensus recommendations that may be useful in the management of CSU.

Allergy rhinitis: similarities and differences between children and adults.

BACKGROUND: Allergic rhinitis (AR) is a highly prevalent disease worldwide. Although a number of studies have described AR, no studies compared children and adult AR populations. The objective was to compare the AR characteristics between two AR cohorts of children and adults. METHODS: Two AR cohorts (children and adults) from Spain were studied through observational cross-sectional multicentre studies. AR was classified based on classical (allergen exposure), original (o-ARIA), and modified (m-ARIA) ARIA criteria. AR was evaluated by Total 4-Symptoms Score (T4SS), and disease severity by Visual Analogue Scale (VAS, 0-100 mm). AR comorbidities were also evaluated. RESULTS: A total of 5,405 patients (1,275 children, 4,130 adults) were studied. According to symptoms duration, intermittent AR was more frequent in children than in adults. Using o-ARIA severity, more children than adults had moderate/severe AR while, using m-ARIA, more children than adults had severe AR. T4SS was higher in adults than in children. Moreover, VAS was also higher in adults than in children. In addition, asthma atopic dermatitis and conjunctivitis were more associated to children than adults with AR, the frequency of this comorbidities increasing according to higher severity. CONCLUSIONS: AR in children was more intermittent, severe, with less symptoms but with more comorbidities than in adults. These results suggest AR has similarities but also significant differences between children and adults.

Allergic rhinitis severity can be assessed using a visual analogue scale in mild, moderate and severe.

BACKGROUND: Allergic rhinitis is a global healthcare problem due to its high prevalence, impact on individuals and socioeconomic burden for the nations. Allergic rhinitis severity evaluation is the key to a correct treatment, prevention of comorbidities and improving the quality of life of patients. This evaluation should be made with a simple, easy, fast but accurate and reliable methodology, both in a primary care and specialist setting. The visual analogue scale (VAS) meets all requirements to be the ideal tool to assess allergic rhinitis severity and has already been validated by using a single cut-off point, but this classification in two degrees of severity suffer from not allocating the patients uniformly and from giving a blind interval to classify the patients when the score is between 5 to 6 cm. METHODOLOGY: The main objective of our study is to describe the optimal cut-off points by using a VAS to discriminate between three degrees of allergic rhinitis severity (mild, moderate, and severe) following the ARIA modified severity criteria that has been previously validated. Sensitivity, specificity, positive and negative predictive values just like receiver operating characteristic curves were used to select the best cut-off values. RESULTS: In a cross-sectional multicentre study with 3,572 patients included we have found that VAS has a significant correlation with nasal symptom score and quality of life and that the best cut-off points to differentiate between mild, moderate an severe allergic rhinitis are a VAS score of 4 and 7, respectively. CONCLUSIONS: Allergic rhinitis severity could be assessed in three degrees by using VAS in a simple, easy, and accurate method.

Management of urticaria: not too complicated, not too simple.

In spite of being an old disease and apparently easy to diagnose, chronic spontaneous urticaria (CSU) is still perceived as an uncontrollable and difficult to manage disease. The perception of the patient is that his/her condition is not well understood and that is suffering from a disorder with hidden causes that doctors are not able to tackle. Sometimes patients go through a number of clinicians until they found some CSU expert who is familiar with the disease. It is surprising that myths and believes with no scientific support still persist. Guidelines are not widely implemented, and recent tools to assess severity are infrequently used. European and American recent guidelines do not agree in several key points related to diagnosis and treatment, which further contributes to confusion. With the aim to clarify some aspects of the CSU picture, a group of allergists and dermatologists from the Spanish Dermatology and Allergy societies developed a Frequent Asked Questions leaflet that could facilitate physicians work in daily practice and contribute to a better knowledge of common clinical scenarios related to patients with CSU.

Assessment of severity and quality of life in chronic urticaria.

Chronic urticaria (CU) is very prevalent in the general population and, despite its low mortality, can have devastating effects on the quality of life (QoL) of those who experience it.Therefore, consensus documents on its classification, diagnosis, and treatment have become a necessity. The intensity of urticaria is currently evaluated using indices such as the Urticaria Activity Score and visual analog scales to assess itch or the degree of itch associated with the use of antihistamines. QoL is evaluated using various generic questionnaires and specific tools for skin disease and for CU. In recent years, attempts have been made to combine these evaluations to create a specific tool that would enable us to simultaneously evaluate the severity of the condition and the impact of symptoms on QoL. One such tool is the Urticaria Severity Score, which also allows us to compare global changes brought about by different treatments.

Use of second generation H1 antihistamines in special situations.

Antihistamine drugs are one of the therapeutic classes most used at world level, at all ages and in multiple situations. Although in general they have a good safety profile, only the more recent drugs (second generation antihistamines) have been studied specifically with regard to the more important safety aspects. Given the variety of antihistamine drugs, they cannot all be considered equivalent in application to various special clinical situations, so that the documented clinical experience must be assessed in each case or, in the absence of such, the particular pharmacological characteristics of each molecule for the purpose of recommendation in these special situations. In general, there are few clinical studies published for groups of patients with kidney or liver failure, with concomitant multiple pathologies (such as cardiac pathology), in extremes of age (paediatrics or geriatrics) and in natural stages such as pregnancy or lactation, but these are normal situations and it is more and more frequent (among the elderly) for antihistamine drugs to be recommended. This review sets out the more relevant details compiled on the use of antihistamines in these special situations.

H1 antihistamines and benzodiazepines. Pharmacological interactions and their impact on cerebral function.

Antihistamines (AH) have been classified into first and second generation according to their pharmacokinetic properties, structural characteristics and adverse effects. The effects on the central nervous system (CNS) are determined basically by their capacity to cross the hematoencephalic barrier and attach to central H1 receptors. Benzodiazepines (BZD) are drugs with effects on the CNS following their union to the specific location of GABA receptors type A. At low doses, the BZD have sedative and anticonvulsive effects, and as the dose increases it leads to sedation, amnesia and finally unconsciousness. Various studies have been made on the possible interaction between the BZD and the AH H1 with special attention to their effect on the CNS. In some cases these were studies to assess the safety of this association and in others, the aim was different: to see if their joint administration gives a better therapeutic result in pathology related with anxiety syndrome or insomnia. In general it can be said that first generation AH interact with the BZD increasing the sedative effects of the latter. However, second generation AH do not increase these sedative effects, which makes them the chosen drugs to treat allergic rhinitis/rhino-conjunctivitis and urticaria in patients also receiving BZD.

Antihistamines in drivers, aircrew and occupations of risk.

The most commonly occurring allergic diseases can involve a daytime drowsiness associated with the condition itself. The antihistamines used in their treatment can also have central effects and affect certain occupations concerned with risk, road safety and maritime and air navigation. Cognitive tests, experimental studies and epidemiological data recommend avoiding 1st generation antihistamines for people who must drive regularly and/or professions concerned with safety. Although there are no comparative studies on real driving between 1st and 2nd generation antihistamines, in this type of patients there should be a preference for prescribing those with least possible central effect, especially those which are a good substrate for transmembrane transporter pumps such as P-glycoprotein and therefore have a low capacity for crossing the hematoencephalic barrier, thus allowing a broader window for therapy. In this sense, bilastine is a good P-glycoprotein substrate and shows good tolerance at CNS level, in both psychometric trials and real driving test protocols, even at double the dose recommended in the technical file.

Left side clot in transit in double-lung transplantation diagnosticated by transesophageal echocardiography: what's next?

A 61-year-old man with no predisposition to thrombosis underwent sequential double lung transplantation without extracorporeal membrane oxygenation (ECMO) support due to terminal stage COPD. After implantation and reperfusion of both lungs, a complete transoesophageal echocardiography study was performed to check the pulmonary venous anastomosis. The study showed a large, heterogeneous, dense, hyperechoic free-floating mass in the left atrium compatible with a clot in transit from the pulmonary circulation. The surgical team were notified of this finding so that they could reopen the anastomosis and remove the clot to prevent a major complication. There were no clinical manifestations when the patient was awakened.

Disease severity impairs sleep quality in allergic rhinitis (The SOMNIAAR study).

BACKGROUND: Sleep is impaired in allergic rhinitis (AR) patients, with subsequent effects on daytime performance and health-related quality of life (QOL). Sleep quality in AR has rarely been considered through validated tools and consensus classifications. OBJECTIVE: To evaluate sleep quality and daytime somnolence in AR patients, and to estimate its relationship to disease severity according to Allergic Rhinitis and Its Impact on Asthma (ARIA) conventional and modified classifications, as well as in terms of QOL and comorbidities. METHODS: Allergic rhinitis adult patients were evaluated through a prospective, observational, multicentre survey in Spain. Symptoms were assessed using the Total Symptoms Score (TSS), specific QOL by the Rhinitis Quality of Life Questionnaire (RQLQ), sleep quality by Pittsburgh scale, and diurnal somnolence by a scale based on Epworth's, all recorded in a unique visit. RESULTS: A total of 2275 patients were included. According to ARIA criteria, 50.2% had persistent and 49.8% intermittent rhinitis, whereas 87.6% were classified as moderate-severe and 12.4% as mild; 52.8% had poor sleep quality, with a global median score for Pittsburgh scale of 6 (normal < 5) and 21.1% suffered from excessive diurnal somnolence. Correlation between Pittsburgh scale and RQLQ was moderate (r = 0.54). Among symptoms, nasal obstruction and concomitant asthma mainly, contributed to bad sleep quality. In a logistic regression model, moderate-severe rhinitis and nasal obstruction were all associated with a worse sleep quality. CONCLUSIONS AND CLINICAL RELEVANCE: Sleep quality is altered in AR patients. Sleep quality was worse in moderate-severe, and particularly in severe AR. Nasal obstruction and RQLQ deterioration are associated with a poorer sleep quality. Sleep impairment is common in allergic rhinitis, particularly in more severe forms. Nasal obstruction and concomitant asthma should be considered as contributing factors. CAPSULE SUMMARY: This is a large epidemiological survey of patients with allergic rhinitis showing a strong relationship between disease severity, as assessed by a consensus classification, and sleep impairment, as measured by a validated sleep quality tool.

Validation of the modified allergic rhinitis and its impact on asthma (ARIA) severity classification in allergic rhinitis children: the PEDRIAL study.

BACKGROUND: A modified allergic rhinitis and its impact on asthma (ARIA) (m-ARIA) criterion to classify the severity of allergic rhinitis (AR) has recently been validated in both treated and untreated adult patients; however, such information in children is lacking. The aim of this study was to validate this m-ARIA severity criterion, which allows for discrimination between moderate and severe AR, in a large pediatric patient sample population. METHODS: The m-ARIA classification categorizes AR severity into mild (no affected items), moderate (1-3 affected items), and severe (all four affected items). We applied this modified criterion to untreated AR pediatric patients aged 6-12 years, through an observational, cross-sectional, and multicenter study. AR symptoms were assessed using the Total Four Symptom Score (T4SS), and the severity was evaluated by both ARIA severity items and visual analogue scale (VAS). RESULTS: Allergic rhinitis pediatric patients (N = 1269) from 271 centers were included. Among them, 59.5% had intermittent and 40.5% persistent disease; 89.9% had moderate/severe AR using the original ARIA (o-ARIA) classification and 59.5% had moderate, while 30.5% had severe AR using the m-ARIA criterion. Using the m-ARIA, significantly higher T4SS and VAS scores were obtained when comparing severe with moderate AR. CONCLUSIONS: The m-ARIA severity classification is a useful clinical tool to discriminate moderate from severe AR among untreated pediatric patients.

Diagnostic utility of components in allergy to Anisakis simplex.

BACKGROUND: In our region, Anisakis allergy is responsible for 8% of acute urticarial reactions, 25% of which progress to anaphylactic shock. The poor specificity of skin tests and in vitro specific immunoglobulin (Ig) E means that Anisakis allergy is frequently overdiagnosed. OBJECTIVE: We studied the diagnostic value of 2 Anisakis allergens: rAni s 1 and rAni s 3. METHODS: Skin tests, the basophil activation test (BAT), and specific IgE determination were performed with rAni s 1 and 3 in 25 patients allergic to Anisakis, 17 atopic controls, and 10 controls with acute urticaria and positive skin test and sIgE results for Anisakis, but no allergy to Anisakis. RESULTS: For rAni s1, skin tests had a sensitivity and specificity of 100% and specific IgE had a sensitivity and specificity of 100% in the atopic control group and 90% in the urticaria control group. BAT had a sensitivity of 96.8% and a specificity of 100% in the atopic control group and 66.7% in the urticaria control group. For rAni s 3, only 1 patient had positive specific IgE results to rAni s 3. All other techniques gave negative results in patients and controls CONCLUSIONS: rAni s 1 is the major allergen of Anisakis and the target allergen when diagnosing allergy to Anisakis, rAni s 3 is not relevant when attempting to explain false-positive results.

Update on the use of ultrasound in the diagnosis and monitoring of the critical patient.

Hemodynamic and respiratory complications are the main causes of morbidity and mortality in in critical care units (CCU). Imaging techniques are a key tool in differential diagnosis and treatment. In the last decade, ultrasound has shown great potential for bedside diagnosis of respiratory disease, as well as for the hemodynamic assessment of critically ill patients. Ultrasound has proven to be a useful guide for identifying the type of shock, estimating cardiac output, guiding fluid therapy and vasoactive drugs, providing security in the performance of percutaneous techniques (thoracentesis, pericardiocentesis, evacuation of abscesses/hematomas), detecting dynamically in real time pulmonary atelectasis and its response to alveolar recruitment maneuvers, and predicting weaning failure from mechanical ventilation. Due to its dynamic nature, simple learning curve and absence of ionizing radiation, it has been incorporated as an essential tool in daily clinical practice in CCUs. The objective of this review is to offer a global vision of the role of ultrasound and its applications in the critically ill patient.