Embryonic-stem-cell-derived mesenchymal stem cells relieve experimental contact urticaria by regulating the functions of mast cells and T cells.

Contact urticaria (CU) is an inflammatory skin disorder triggered by specific substances upon skin contact, leading to immediate acute or chronic manifestations characterized by swelling and redness. While mesenchymal stem cells (MSCs) are increasingly recognized for their therapeutic potential in immune diseases, research on the efficacy and mechanisms of stem cell therapy for urticaria remains scarce. This study investigates the regulatory role of embryonic-stem-cell-derived multipotent MSCs (M-MSCs) administered in a CU mouse model. Therapeutic effects of M-MSC administration were assessed in a Trimellitic anhydride-induced contact urticaria model, revealing significant inhibition of urticarial reactions, including ear swelling, itchiness, and skin lesion. Moreover, M-MSC administration exerted control over effector T cell activities in major lymphoid and peripheral tissues, while also suppressing mast cell degranulation in peripheral tissues. Notably, the inhibitory effects mediated by M-MSCs were found to be TGF-ß-dependent. Our study demonstrates the capacity of M-MSCs to regulate contact urticaria in a murine model, harmonizing the activation of inflammatory T cells and mast cells. Additionally, we suggest that TGF-ß derived from M-MSCs could play a pivotal role as an inhibitory mechanism in contact urticaria.

[Effect of acupuncture pretreatment of "Quchi"(LI11) and "Xuehai" (SP10) on mast cells and IL-33/ST2 in rats with urticaria].

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment at "Quchi "(LI11) and "Xuehai "(SP10) on expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and mast cell degranulation in sensitive area of skin tissue in rats with urticaria, so as to explore its mechanisms underlying prevention of urticaria. METHODS: A total of 32 male SD rats were randomly divided into blank control, model, EA preconditioning and medication groups, with 8 rats in each group. The urticaria model was established by topical injection of the prepared anti-ovalbumin serum (foreign serum, 0.1 mL/spot) along the bilateral sides of the spinal column on the back, followed by injection of mixture solution of ovalbumin, 0.5% evans blue and normal saline via the tail vein 48 h later. EA intervention (2 Hz/15 Hz, 1 mA) was applied to bilateral LI11 and SP10 for 20 min, once daily for 7 d before modeling.Back sensitization was started from the 5th day on. Rats of the medication group received gavage of loratadine, and those of the model group received gavage of the same volume of normal saline. The diameter of evans blue spots at the back skin tissue was measured; the histopathological changes of the blue spot tissues were observed by light microscope after H.E. staining. The state of degranulation of mast cells in the subcutaneous loose connective tissue was observed by using toluidine blue staining. Serum IgE and histamine contents were detected by ELISA, and the immunoactivity of IL-33 and ST2 in the skin and subcutaneous tissues of the sensitized spots (evans blue exudation spots) was observed by immunohistochemistry. RESULTS: Compared with the blank control group, the diameter of evans blue spot, degranulation rate of mast cells, serum IgE and histamine contents, and the immunoactivity of IL-33 and ST2 in the evans blue exudation spot tissues were significantly increased in the model group (P<0.01). In comparison with the model group, the increase of the above-mentioned indexes was reversed in both EA and medication groups (P<0.01，P<0.05). No significant differences were found between the EA and medication groups in down-regulating the levels of the 6 indexes. H.E. staining of the blue spot tissues of rats in the model group showed incomplete structure of the epidermal layer of the skin, unclear interface of tissues, incomplete keratinization, chaotic epidermal cells, disorderly arrangement of fibers in the dermis, and infiltration of inflammatory cells and edema, which was relatively milder in the EA and medication groups. CONCLUSION: EA preconditioning can prevent urticaria (reduce size and sensitive reactions) in rats, which may be associated with its functions in lowering the level of IgE through inhibiting IL-33 and ST2.

A focused report on progestogen hypersensitivity.

INTRODUCTION: Progestogen Hypersensitivity (PH) is caused by increased sensitivity to either exogenous or endogenous progestogens. It is characterized by recurrent cutaneous eruptions including erythema multiforme, eczema, urticaria, and angioedema, which may be associated with systemic symptoms including asthma and anaphylaxis. AREAS COVERED: Symptoms may be persistent or cyclical, coinciding with progestogen levels. With increased use of oral contraceptives and hormonal treatments for fertility, the prevalence of PH is expected to continuously increase. Several proposed immunological mechanisms, diagnostics, and treatment modalities have been proposed. Most treatments focus on suppressing ovulation and progesterone secretion or inducing tolerance through progesterone desensitization. EXPERT OPINION: Although there has been increased recognition both clinically and in the medical literature, there is still a general lack of knowledge of PH and its clinical features in the medical community. An improved understanding of the underlying pathophysiology as well as more available commercial testis, such as ELISA that accurately measures specific IgE to progesterone, are expected to broaden and improve opportunities for disease recognition and symptom control. It is essential for physicians across specialties to recognize how to diagnose PH and either manage this condition or refer these patients to a specialist with experience treating PH.

CME suggestions for pediatricians, allergists, and dermatologists, directed by an online survey on urticaria knowledge.

BACKGROUND: The Mexican Guidelines for the diagnosis and treatment of urticaria have been published. Just before their launch, physicians' knowledge was explored relating to key issues of the guidelines. OBJECTIVE: The aim of this study was to investigate the opinion of medical specialists concerning urticaria management. METHODS: A SurveyMonkey® survey was sent out to board-certified physicians of three medical specialties treating urticaria. Replies were analyzed per specialty against the evidence-based recommendations. RESULTS: Sixty-five allergists (ALLERG), 24 dermatologists (DERM), and 120 pediatricians (PED) sent their replies. As for diagnosis: ALERG 42% and PED 76% believe cutaneous mastocytosis, urticarial vasculitis, and hereditary angioedema are forms of urticaria, versus DERM 29% (P < 0.005). Most of the specialties find that the clinical history and physical examination are enough to diagnose acute urticaria, except DERM 45% (P < 0.01). DERM 45% believe laboratory-tests are necessary, as opposed to <15% ALLERG-PED (P < 0.005). However, PED 69% did not know that the most frequent cause of acute urticaria in children is infections, versus ALLERG-DERM 30% (P < 0.005). Many erroneously do laboratory testing in physical urticaria and ALLERG 51%, DERM 59%, and PED 37% do extensive laboratory testing in chronic spontaneous urticaria (CSU); many more PED 59% take Immunoglobulin G (IgG) against foods (P < 0.005). More than half of non-allergists do not know about autologous serum testing nor autoimmunity (P < 0.05). As for treatment, there were a few major gaps: when CSU was controlled, >75% prescribed antihistamines pro re nata, and >85% gave first-generation antiH1 for insomnia. Finally, >40% of DERM did not know that cyclosporine A, omalizumab, or other immunosuppressants could be used in recalcitrant cases. CONCLUSION: Specialty-specific continuous medical education might enhance urticaria management.

Pomalidomide desensitization for hypersensitivity: A case report.

INTRODUCTION: Pomalidomide is an immunomodulating agent that is used to treat relapsed and/or refractory multiple myeloma. Although the incidence of hypersensitivity with pomalidomide is not well documented, the most common type of hypersensitivity involves a cutaneous reaction. Previous reports have successfully utilized a desensitization protocol in patients who developed hypersensitivity to pomalidomide. Here we describe a case of a patient who developed urticaria on pomalidomide and successfully underwent a desensitization using the previously reported method in a case report. CASE REPORT: A 68-year-old woman with relapsed multiple myeloma and no known drug allergies developed urticaria a day after taking the first dose of pomalidomide. MANAGEMENT AND OUTCOME: The patient underwent a 10-step desensitization process in the medical intensive care unit without any reported adverse events. The following day in the medical intensive care unit, the patient was able to tolerate a full dose of pomalidomide with no further reactions and was discharged with instructions to take a full dose of pomalidomide daily for 21 days out of a 28-day cycle. The patient was followed up in the outpatient clinic and noted no further reactions from pomalidomide at the three-month visit. DISCUSSION: The 10-step desensitization protocol with pomalidomide was well tolerated in the patient with hypersensitivity to pomalidomide. Whether this approach would work in patients with more severe reactions such as anaphylaxis and angioedema is still unknown.

Effects of RNA interference-mediated E-selectin gene silencing on cell adhesion molecule expression and cell-cell adhesion in vascular endothelial cells in mice with immunologic contact urticaria.

Contact urticaria is recognized as the wheal and flare reaction at a site from direct contact with a chemical or protein agent. Ongoing studies have proposed that gene silencing may have a promising future in finding optimal treatment of a variety of disease; hence, the aim of the study was to investigate the effect of RNA interference-mediated E-selectin ( SELE) gene silencing on cell adhesion molecule expression and on cell-cell adhesion in vascular endothelial cells (VECs) in a mouse model of immunologic contact urticaria (ICU). Following the successful establishment of mouse models of ICU induced by antidinitrophenol immunoglobulin E (IgE) combining 2,4-dinitrofluorobenzene challenge, enzyme-linked immunosorbent assay and immunohistochemistry were used to measure the levels of IgE, interleukin 4 (IL-4), interferon-γ (IFN-γ), and histamine as well as the positive expression rate of SELE, respectively. The siRNA- SELE vector was constructed and transfection efficiency was estimated prior to performing quantitative reverse-transcription polymerase chain reaction and Western blot assay to determine the relative expression of SELE, eosinophil cationic protein (ECP), intercellular adhesion molecule 1 (ICAM-1), L-selectin (CD62L), and the alpha chain of leukocyte function-associated antigen-1 (CD11a). Adhesion assay was then performed to assess the cell adhesion ability in VECs. Elevated levels of IgE, IL-4, IFN-γ, and histamine and increased positive expression rate of SELE were indicative of successful establishment of mouse models of ICU. Furthermore, the relative expression levels of SELE, ECP, ICAM-1, CD62L, and CD11a were highest in the OE- SELE group. Besides, cell adhesion ability of VECs was notably promoted. Collectively, the current study define the potential role of SELE silencing as an inhibitor to ICU development by inhibiting cell adhesion ability of VECs.

Dermatologic manifestations in spaceflight: a review.

With manned missions to Mars on the horizon, understanding and preparing for the medical conditions these astronauts might face becomes vital. According to the literature, the most commonly reported medical events in space are dermatological in nature. Dermatologic conditions rarely threaten an astronaut's life or the mission. However, manifestations and management of dermatologic events become an important consideration in anticipation of spaceflights to Mars and beyond. Given the limited number of articles written about dermatological conditions in this specific population, this review summarizes current knowledge related to dermatology in space. Overall, common dermatologic conditions found during spaceflight include viral reactivations, contact dermatitis or eczematous patches, and skin infections. Diagnosis and treatment can be difficult given the lack of resources in space as well as the hazards and side effects of certain treatments. In this review article we aim to summarize common skin changes induced by spaceflight, describe previously reported skin conditions including current treatment options, explore the risk of skin cancer in this unique population, and address the challenge of remote diagnosis.

Urticaria aguda y tratamiento ambulatorio indicado en emergencia de dos hospitales de atención pediátrica / Acute urticarial and outpatient treatment given in two pediatric care hospitals

Antecedentes: La urticaria aguda es una dermatosis frecuente, se calcula que ocurre en 20% de la población mundial. La tasa de preva-lencia varía de acuerdo con la población de cada país entre 3.4 y 6.4%. En Honduras en el Instituto Hondureño de Seguridad Social (IHSS), la urticaria aguda es la cuarta causa más frecuente de dermatosis en consulta externa dermatológica pediátrica. Objetivo: Determi-nar las características clínicas-sociodemográ -cas y el manejo en salas de Emergencia del Hospital Nacional Mario Catarino Rivas (HNMCR) y IHSS ambos hospitales en SPS, en el período enero 2016­julio 2017. Pacientes y Métodos: El diseño de la investigación fue transversal observacional, con alcance descrip-tivo. Se incluyeron 83 pacientes en edad pediá-trica con diagnóstico de urticaria aguda, evaluados en las emergencias del IHSS y HNMCR. Resultados: El grupo etario y raza afectados fueron los lactantes menores 68.67% (n=57) y raza mestiza 86.75% (n=72). No tenían antecedentes inmunoalérgicos 63.86% (n=53). El alimento relacionado con urticaria fue el huevo 9.64% (n=8) y entre los medicamentos; los antibióticos 23.08% (n=19). El tratamiento administrado con mayor frecuencia fue la doble terapia 65.21% (n=30) y se ingresaron 17 pacientes (20.48%). Conclusión: El manejo terapéutico y los criterios de ingreso utilizado en el servicio de emergencia no siguen los lineamientos de guías internacionales...(AU)

Potential blood biomarkers in chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is a mast cell-driven disease that is defined as the recurrence of weals, angioedema or both for > 6 weeks due to known or unknown causes. As of yet, disease diagnosis is purely clinical. Objective tools are needed to monitor the activity of CSU and the efficacy of treatment. Recently, several reports have suggested that blood parameters may be considered as potential disease-related biomarkers. Here, we reviewed available literature on blood biomarkers for CSU diagnosis, activity monitoring, duration, patient subgroup allocation or response to treatment. We performed a PubMed, Google Scholar and Web of Science search and identified and analysed 151 reports published prior to January 2016. We found strong evidence for significant differences between patients with CSU and healthy controls in blood levels or values of D-dimer, C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9), mean platelet volume (MPV), factor VIIa, prothrombin fragment 1 + 2 (F1 + 2), tumour necrosis factor, dehydroepiandrosterone sulphate and vitamin D. Also, there is strong evidence for a significant association between CSU activity and blood levels or values of D-dimer, F1 + 2, CRP, IL-6 and MPV. Strong evidence for reduced basophil count and high levels of IgG anti-FcεRI in the subgroup of CSU patients with positive autologous serum skin test was shown. In contrast, the evidence for all reported blood biomarkers for differentiating CSU from other diseases, or a role in prognosis, is weak, inconsistent or non-existent. Taken together, we identified 10 biomarkers that are supported by strong evidence for distinguishing patients with CSU from healthy controls, or for measuring CSU activity. There is a need for further research to identify biomarkers that predict outcome or treatment response in CSU.

Altered Systemic Adipokines in Patients with Chronic Urticaria.

BACKGROUND: Increasing evidence suggests that adipokines affect immune responses and chronic urticaria (CU) is associated with an altered immune response related to chronic systemic inflammation. Our objectives were to investigate whether adipokines are involved in CU pathogenesis and to outline relationships between adipokines and urticaria severity and quality of life. METHODS: Serum adiponectin, leptin, lipocalin-2 (LCN2), interleukin (IL)-10, IL-6, and tumor necrosis factor (TNF)-α concentrations were measured by enzyme-linked immunosorbent assays in 191 CU patients and 89 healthy controls. The effect of LCN2 on N-formyl-methionine-leucine-phenylalanine (fMLP)-induced neutrophil chemotaxis was assessed using migration assays. CU severity was assessed based on the urticaria activity score (UAS). To explore relationships between adipokines and UAS and the chronic urticaria-specific quality of life (CU-QoL) questionnaire, a structural equation model was used. RESULTS: Mean levels of serum LCN2, TNF-α, IL-6, and IL-10 were significantly higher in CU patients than in controls. Adiponectin levels were significantly lower in patients with CU than in controls. While serum IL-6 levels were significantly higher in refractory CU patients, compared to responsive CU individuals, LCN2 levels were significantly lower. LCN2 inhibited fMLP-induced neutrophil migration. LCN2 showed a direct relationship with UAS (ß = -0.274, p < 0.001), and UAS was found to contribute to CU-QoL (ß = 0.417, p < 0.001). CONCLUSIONS: Our results highlighted an imbalance in pro- and anti-inflammatory adipokines in CU patients. We suggest that LCN2 could be a differential marker for disease activity and the clinical responses to antihistamine treatment in CU patients. Modulation of systemic inflammation may be a therapeutic strategy for treating severe, refractory CU.

Correlation between the histopathology of chronic urticaria and its clinical picture

Abstract BACKGROUND: Chronic urticaria is characterized by transient, pruritic lesions of varying sizes, with central pallor and well-defined edges, with disease duration longer than six weeks. Its cellular infiltrate consists of neutrophils, lymphocytes and eosinophils. There is a subgroup of patients with eosinophilic or neutrophilic urticaria, resistant to the treatment with antihistamines, but that respond to a combination of antihistamine with other drugs. OBJECTIVE: To evaluate the present infiltration in chronic urticaria biopsies and correlate it with the clinical disease activity and response to treatment. METHODS: Forty-one patients with chronic urticaria were classified according to the score of severity of the disease, response to treatment and type of perivascular infiltrate. Inflammatory infiltrates were divided in eosinophilic (46.30%), neutrophilic and mixed. RESULTS: An association was found between the eosinophilic infiltrate and clinical scores of greater severity (p = 0.002). CONCLUSION: This association shows that the eosinophilic inflammatory infiltrates denote high clinical activity, which means more severe and exuberant clinical pictures of the disease.

Itch Management: Physical Approaches (UV Phototherapy, Acupuncture).

BACKGROUND: Physical therapies refer to non-medical treatment strategies, including surgery, cryotherapy, UV phototherapy, and acupuncture. Most physical approaches are inappropriate in the context of itch. UV phototherapy and acupuncture may be effective in the management of itch. METHODS: A literature search was performed using MEDLINE and EMBASE. Bibliographies were reviewed for relevant articles. RESULTS: Narrowband UVB (311-313 nm) and UVA1 (340-400 nm) are equally effective in managing atopic dermatitis and associated itch. The efficacy of broadband UVB in reducing uraemic itch has been demonstrated in a series of randomised controlled trials, but more recent studies have failed to reproduce these results. Non-randomised, uncontrolled studies and case series suggest that UV is effective in managing itch associated with cholestasis, chronic urticaria, prurigo, cutaneous T-cell lymphoma, aquagenic itch, and scleroderma. UV phototherapy is well tolerated, and no significant relationship between UVB therapy and skin cancer has been found. Experimentally, acupuncture has been shown to reduce allergen-related itch, although this finding has been limited by the small number of studies, inconsistency in agreement on acupuncture sites and study design, small sample sizes, and limited follow-up. CONCLUSIONS: UV phototherapy is an effective treatment for itch associated with atopic dermatitis. UVB may be effective in managing itch associated with end-stage kidney disease, cholestasis, chronic urticaria, prurigo, cutaneous T-cell lymphoma, aquagenic itch, and scleroderma. Phototherapy should be combined with standard first-line therapies. Insufficient evidence exists to justify acupuncture as a physical therapy for itch. Further well-designed studies are required to establish the effectiveness of physical therapies in managing itch.

Reacción sistémica tras la ingesta de una oruga procesionaria del pino: ¿Manejo conservador? / Systemic reaction after pine processionary caterpillar ingestion: Conservative management?

La oruga procesionaria del pino, forma larvaria de la mariposa nocturna Thaumetopoea pityocampa, es una de las principales plagas forestales del sur de Europa. Con frecuencia, estas orugas producen reacciones locales en humanos debidas a los pelillos urticantes microscópicos que las recubren. La mayoría de los síntomas ocasionados son cutáneos, como urticaria aguda, y son mucho más infrecuentes las reacciones sistémicas. Se presenta un caso de reacción sistémica, con edema orofacial, babeo y urticaria tras la ingesta de una oruga procesionaria del pino en un lactante de 11 meses, en el cual el tratamiento farmacológico fue suficiente para la resolución de los síntomas. No tuvo, en ningún momento, compromiso de la vía aérea ni otros datos de anafilaxia, por lo que se desestimaron actuaciones más agresivas, como intubación orotraqueal, endoscopía o laringoscopía.

The larval form of the moth Thaumetopoea pityocampa, known as pine processionary caterpillar, is one of the main forest pests in southern Europe. Often, these caterpillars cause local reactions in humans, due to their microscopic stinging hairs. Most symptoms affect skin, in form of acute urticaria. Systemic reactions are rare. An eleven month old infant with a systemic reaction after ingestion of a pine processionary caterpillar is presented. The boy reached the Emergency Room with orofacial edema, drooling and urticaria. Drug treatment was enough to resolve the symptoms. The patient did not present airway commitment, nor anaphylaxis data at any moment, so more aggressive actions, such as endotracheal intubation, endoscopy or laryngoscopy, were rejected.

Chronic Spontaneous Urticaria (CSU): Canadian Dermatologists' Perspective.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a skin disorder that is said to be "frustrating" and "difficult to treat." It is characterized by recurrent hives for more than 6 weeks, and is further divided into spontaneous or inducible by physical stimuli.(1) To better understand dermatologists' perspective of this disorder, a survey was conducted with Canadian dermatologists. METHODS: A detailed online practice survey was sent to all currently practicing Canadian dermatologists. RESULTS: In all, 80 responses were received (response rate of 20%). Most respondents in Canada had treated patients with CSU (98.4%), with many of the patients having the disease last over 6 months (86.6%). A majority of the patients were female, with 84.1% of the respondents having over 50% of their patients as female. Most patients were over the age of 30 (74.2%). Of dermatologists, 85.7% felt that investigations were unhelpful in diagnosing CSU in a patient. Of respondents, 37.1% were not satisfied with current treatment methods of CSU, and 43.6% somewhat satisfied. Popular therapies included H1 and H2 antihistamines, oral corticosteroids, and montelukast. There were 16.1% of dermatologists who had over 50% of their patients refractory to treatment. CONCLUSIONS: There was a clear demographic preponderance for CSU patients with a majority as female over age 30. Investigations ordered for CSU patients do not seem to be helpful among dermatologists. Satisfaction with current therapies and investigations was quite low among Canadian dermatologists, suggesting new therapies are indicated.

Correlation between the histopathology of chronic urticaria and its clinical picture.

BACKGROUND:: Chronic urticaria is characterized by transient, pruritic lesions of varying sizes, with central pallor and well-defined edges, with disease duration longer than six weeks. Its cellular infiltrate consists of neutrophils, lymphocytes and eosinophils. There is a subgroup of patients with eosinophilic or neutrophilic urticaria, resistant to the treatment with antihistamines, but that respond to a combination of antihistamine with other drugs. OBJECTIVE:: To evaluate the present infiltration in chronic urticaria biopsies and correlate it with the clinical disease activity and response to treatment. METHODS:: Forty-one patients with chronic urticaria were classified according to the score of severity of the disease, response to treatment and type of perivascular infiltrate. Inflammatory infiltrates were divided in eosinophilic (46.30%), neutrophilic and mixed. RESULTS:: An association was found between the eosinophilic infiltrate and clinical scores of greater severity (p = 0.002). CONCLUSION:: This association shows that the eosinophilic inflammatory infiltrates denote high clinical activity, which means more severe and exuberant clinical pictures of the disease.

Apis mellificaem tratamento de urticária crônica e angioedema: relato de caso / Apis mellifica treatment of chronic urticaria and angioedema: case report

É relatado um caso de paciente com quadro de urticária crônica e angioedema com mais de 18 anos de evolução. Mal controle de sintomas com tratamento convencional e visitas cada vez mais frequentes ao pronto socorro deterioravam sua qualidade de vida e traziam insegurança devido ao potencial de gravidade do quadro. Em sua primeira consulta homeopática foi verificado alto grau de semelhança sintomática com a patogenesia de Apis mellifica, o qual foi introduzido e modificou a história de vida da paciente em questão, com excelente controle do quadro clínico. Foi realizada revisão da literatura sobre urticária e o policresto Apis mellifica. Este relato tem como objetivos chamar atenção para a existência e importância de recursos terapêuticos não convencionais, como é o caso da homeopatia, e também compartilhar com os colegas homeopatas a condução do caso, desde o diagnóstico e escolha do medicamento, ao seguimento da paciente.

We report the case of a patient with chronic urticaria and angioedema for more than 18 years. The symptoms were poorly checked with conventional treatment and increasingly frequent visits to the emergency department seriously affected the patient’s quality of life, in addition to making her feel insecure about the severity of her condition. During the first homeopathic consultation we detected a high degree of similarity with the pathogenetic symptoms of Apis mellifica. The remedy was prescribed and changed the patient’s life history, achieving excellent control of her clinical condition. A literature review was performed on urticaria and polycrest medicine Apis mellifica. The aim of this case report is to call the attention to the availability and relevance of non-conventional therapeutic resources, such as homeopathy, and to share with colleagues aspects of the case management from diagnosis and medicine selection to follow up.

Management of chronic spontaneous urticaria in the elderly.

The guidelines for the management of urticaria in adults and children have been revised and updated recently. However, there are few data in the literature concerning several aspects of this disease in the elderly (e.g., epidemiology, etiopathogenesis, clinical aspects, association with co-morbidities, efficacy and safety profiles of treatments, and management strategies). This is an obvious deficiency in the data, as this disease causes a deterioration in quality of life, affecting the quality of sleep, everyday life habits and activities, and inducing severe disability. Chronic spontaneous urticaria (CSU) can also be associated with internal, infectious, autoimmune, or neoplastic diseases. It is therefore necessary to pay particular attention to these clinical issues through appropriate clinical examinations. At the same time, the specific features of medications used to treat CSU in the elderly should be carefully evaluated, as its pharmacological treatment raises a number of problems related both to the clinical condition of the patient and to concomitant diseases, as well as to the polypharmacotherapy, which is common in older subjects and may cause safety problems because of the drug interactions. Non-sedating new-generation antihistamines are the mainstay treatment of CSU for the elderly. The efficacy and safety of alternative treatment options have not been assessed in the geriatric population with CSU; corticosteroids and cyclosporine (ciclosporin) should be used by this population with extreme caution. Similarly, there are no data regarding the actual safety profile of the new-generation antihistamines at higher doses than those recommended in elderly patients.

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.