Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome in a 15-year-old male, responsive to high-dose fexofenadine.

We describe an unusual presentation of Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome in a 15-year-old male, recalcitrant to low-dose anti-histamines, which subsequently responded to high-dose fexofenadine.

Current and future management of chronic spontaneous urticaria and chronic inducible urticaria.

Background: Chronic urticaria (CU), characterized by ≥6 weeks of intense pruritus, remains a debilitating condition for patients. New and safe treatments are needed to manage CU recalcitrant to standard therapy. Objective: A review of the current literature of standard and novel therapeutics in the management of CU was conducted. Methods: A literature search via a medical literature data base and clinical trial data base was conducted to identify treatment options for CU and current clinical trials. Results: Second-generation antihistamines, omalizumab, and cyclosporine remain the most proven therapeutic options for CU. Dupilumab, mepolizumab, benralizumab, tezepelumab, and CDX-0159 are all undergoing clinical trials for CU. Although ligelizumab demonstrated initial promising results, a phase III study was discontinued due to a nonsuperior clinical impact compared with omalizumab. Conclusion: Novel therapies are needed for the treatment of recalcitrant CU. With a deeper understanding of the pathophysiology of CU, promising therapeutics are in clinical trials for CU.

Clinical experience of a specialized urticaria outpatient clinic from a Portuguese UCARE.

Summary: Background. Chronic urticaria (CU) is a frequent disease, with a prevalence of at least 1%. It is characterized by pruritic wheals, angioedema or both for a period longer than 6 weeks. Objective. Identify the demographic, clinical, laboratory and therapeutic profile of patients treated in a Portuguese Urticaria Center of Reference and Excellence (UCARE) and compare it with international series. Methods. Retrospective analysis of database of patients observed in a specialized urticaria outpatient clinic, from January 2017 through September 2019, of a UCARE center in Portugal. Demographic and clinical features, laboratory findings and pharmacological treatment were obtained from the records. Descriptive analyses were performed for all variables. Chi square and fisher's exact tests were applied to analyze the independence of variables and the fit of distribution. P less than 0.05 was considered significant. Results. During this period, 477 patients were observed, of whom 429 (90%) were diagnosed with chronic urticaria. Mean age (years) at the onset of symptoms was 43.7 (standard deviation (SD) 17.6, range 6-88) and at diagnosis 46.7 (SD 17.8, range 6-88) resulting in an average diagnostic delay of 3 years (range 0-25). Median follow-up period since first attendance in the specialized outpatient clinic was 1.7 years (interquartile range (IQR) 0.79, range 0.1-2.75) . Concerning the whole group of CU patients, 347 (81%) had chronic spontaneous urticaria (CSU) - 79% female, 39 (9%) had isolated chronic inducible urticaria (CIndU) and 43 (10%) had CSU with CIndU. Autologous serum skin test (ASST) was done in 76 patients (positive in 24 (32%)) and basophil activation test (BAT) was done in 38 (positive in 13 (34%)). At the moment of study, 204 (48%) of CU patients were medicated with a second-generation H1-antihistamine (sgAH) daily (first-line therapy), 99 (23%) with sgAH up to four times the standard dose (second-line therapy) and 126 (29%) with omalizumab (third-line therapy). Additionally, 7 (2%) patients were completing a short course of systemic corticosteroids for management of disease exacerbation. Disease control was achieved in 316 of CSU patients (81%). Conclusions. Referral to a specialized urticaria outpatient clinic is important for a proper assessment of the disease and adequately symptom control.

Allergic Rhinitis.

Allergic rhinitis (AR) affects more than 400 million people worldwide, making it 1 of the most prevalent chronic diseases. Childhood AR is increasing, and almost half of patients with AR develop symptoms before age 6 years. Although a diagnosis of AR is associated with higher socioeconomic status, underserved and urban populations have more indoor aeroallergen sensitizations and are likely underdiagnosed with AR, further exacerbating health-care disparities. AR negatively impacts quality of life, school performance, and overall health outcomes. Untreated AR in children increases the risk for poor asthma control, increased asthma severity, and exacerbations. Many patients believe that they have seasonal allergies only but in reality have both perennial and seasonal AR, which may change the approach to allergen avoidance measures and treatment recommendations. Pharmacotherapy of AR has expanded, with many intranasal corticosteroids, intranasal antihistamines, and second-generation oral antihistamines approved for pediatric use. Allergen immunotherapy, including both subcutaneous and sublingual forms, are approved for children and are disease modifying, potentially reducing further allergen sensitization and progression to asthma. Many of the currently available biological therapies indicated for pediatric asthma and/or atopic diseases reduce AR symptoms as well. Children with moderate to severe or refractory AR or those with comorbidities should be referred to allergists for diagnostic testing and expanded management options, including immunotherapy and potential biological treatment.

S3 Guideline Urticaria. Part 2: Treatment of urticaria - German-language adaptation of the international S3 guideline.

This publication is the second part of the German-language S3 guideline on urticaria. It covers the management of urticaria and should be used together with Part 1 of the guideline on classification and diagnosis. This publication was prepared according to the criteria of the AWMF on the basis of the international English-language S3 guideline with special consideration of health system conditions in German-speaking countries. Chronic urticaria has a high impact on the quality of life and daily activities of patients. Therefore, if causal factors cannot be eliminated, effective symptomatic treatment is necessary. The recommended first-line treatment is to administer new generation, non-sedating H1 antihistamines. If the standard dose is not sufficiently effective, the dose should be increased up to fourfold. For patients who do not respond to this treatment, the second-line treatment in addition to antihistamines in the treatment algorithm is omalizumab and, if this treatment fails, ciclosporin. Other low-evidence therapeutic agents should only be used if all treatments in the treatment algorithm agreed upon by the guideline group fail. Both the benefit-risk profile and cost should be considered. Corticosteroids are not recommended for long-term treatment due to their inevitable severe side effects.

Risk factors of uncontrolled symptoms using the standard dose of second-generation H1 -antihistamines in chronic spontaneous urticaria children.

BACKGROUND: A standard dose of second-generation H1 -antihistamines is recommended as the first-line treatment of chronic spontaneous urticaria (CSU), previous studies have found that approximately 20-50% of CSU children fail to control their symptoms and required step-up treatments. OBJECTIVE: To evaluate the predictors of uncontrolled symptoms with first-line medication and describe the treatment outcomes of CSU children in the southern region of Thailand. METHODS: This retrospective chart review of CSU patients, aged 2-18 years, who were initially treated with the standard dose of second-generation H1 -antihistamine at the Pediatric Allergy Clinic, Songkhlanagarind Hospital, from January 2008 to July 2018. The data were collected at the initial visit (demographic data, onset of rash, frequency of urticaria, presence of angioedema, previous resolved CU, laboratory investigation results) and follow-up visits (treatment outcome, time to controlled urticaria). RESULTS: The medical records of 192 CSU children were reviewed; their median age were 8.5 years and the mean frequency of rash was 4 days/week. Forty-seven children (24.4%) fail to controlled symptoms with a standard dose of second -generation H1 -antihistamines and a factor significantly associated was frequency of rash for more than 4 days per week (OR = 4.36, P < 0.001). The median time to controlled urticaria was 1.28 months. CONCLUSIONS: Most of CSU children in the southern region of Thailand experienced controlled symptoms with a standard dose of second-generation H1 -antihistamines, and the frequency of urticaria for more than 4 days per week was a factor associated with uncontrolled symptoms that regimen.

Improving the Quality of Life in the Management of Allergic Rhinitis: New Perspective on Cetirizine.

BACKGROUND: Allergic rhinitis (AR) is associated with disturbed sleep and subsequent functioning, and an impaired quality of life (QoL). The symptoms of AR exhibit prominent circadian variations, with symptoms being more common at the night-time or early morning. Addressing these allergy-related sleep issues, impaired QoL, and circadian variation in symptoms is important from the patient perspective and should be considered in the management of AR. OBJECTIVE: To review the efficacy of cetirizine, a second-generation antihistamine and selective H1-receptor antagonist, in relation to improvement in the QoL of the patients, addressing the sleep disturbances and circadian variations in the symptoms of AR in clinical practice, and establishing its role as a contemporary antihistamine for the management of AR compared to newer antihistamines. METHODS: Systematic literature review of the databases such as PubMed/MEDLINE, Google Scholar, and the Cochrane Central Register of Controlled Trials from 1990 to 2020. RESULTS: The symptoms of AR exhibited a circadian variation, with symptoms being worse during the night and early morning. The patients with AR encountered several sleep-related symptoms, including poor sleep quality, daytime somnolence, fatigue, and impaired productivity and QoL. Impaired QoL in AR was related to the disease severity. Administration of cetirizine at bedtime provides effective control of sleep impairment and symptoms of AR, besides improving the QoL. The efficacy of cetirizine has been demonstrated to be superior or comparable to the newer second-generation antihistamines. Cetirizine exhibits a tolerability profile comparable to the newer antihistamines. CONCLUSION: With long years of clinical experience and a good tolerability profile, cetirizine represents a valuable therapeutic option for the management of AR, even 30 years after its introduction. Cetirizine is included in the National List of Essential Medicines of India for the management of allergic disorders in view of its established efficacy and safety profile as well as being a cost-effective option.

Efficacy and Safety of Up-dosing Antihistamines in Chronic Spontaneous Urticaria: A Systematic Review of the Literature.

BACKGROUND AND OBJECTIVES: According to current guidelines, oral antihistamines are the first-line treatment for chronic spontaneous urticaria (CSU). Up-dosing antihistamines to 4-fold the licensed dose is recommended if control is not achieved. Such indications are based mainly on expert opinion. Objectives: To critically review and analyze clinical evidence on the efficacy and safety of higher-than-licensed dosage of second-generation oral antihistamines in the treatment of CSU. MATERIAL AND METHODS: A systematic literature review was performed following a sensitive search strategy. All articles published in PubMed, EMBASE, and the Cochrane Library between 1961 and October 2018 were examined. Publications with CSU patients prescribed secondgeneration antihistamines in monotherapy compared with placebo, licensed dosages, and/or higher dosages were included. Articles were evaluated by peer reviewers. Quality was evaluated using the Jadad and Oxford scores. RESULTS: We identified 337 articles, of which 14 were included in the final evaluation (fexofenadine, 6; cetirizine, 2; levocetirizine and desloratadine, 1; levocetirizine, 1; rupatadine, 2; ebastine, 1; and bilastine, 1). Only 5 studies were placebo-controlled. The number of patients included ranged from 20 to 439. The observation lapse was ≤16 weeks. High fexofenadine doses produced a significant dosedependent response and controlled urticaria in most patients. Cetirizine, levocetirizine, rupatadine, and bilastine were more effective in up-dosing. The most frequent adverse events were headache and drowsiness. CONCLUSION: The low quality and heterogeneity of the articles reviewed made it impossible to reach robust conclusions and reveal the need for large-scale randomized clinical trials.

Antihistamines: ABC for the pediatricians.

Antihistamines are currently one of the most commonly administered drugs in children. They are used to treat symptoms that depend on histamine release, namely allergic diseases, such as rhinitis, asthma, urticaria, and anaphylaxis. It is possible to distinguish first- and second-generation antihistamines. Pharmacological effects and therapeutic indications are similar, but second-generation antihistamines have fewer adverse effects because they are more selective for peripheral H1 receptors. Although they have been on the market for several years, there are still many adverse effects linked to the antihistamine safety profile, especially in the first years of life. Thus, many antihistamines are prescribed off-label, especially in children younger than 2 years of age, which is the age-group where most of the data on drug safety are lacking and many antihistamines are not recommended. This article aims to provide a practical update on the use of antihistamines in children.

Medication used to control symptoms of chronic urticaria in children.

BACKGROUND: A number of guidelines for management of CU were established based on evidences in adults. In children, the response to CU treatment was not widely studied. OBJECTIVE: To investigate the medications used to control symptoms of CU in children and to identify factors associated with time to control CU. METHODS: Medical records of children with controlled CU visiting Allergy clinic, Siriraj hospital were examined. Controlled CU was defined as no urticarial lesion while the patients used the same daily medications over 8-12 weeks. Demographic data, clinical progression of CU and medications used in each visit were recorded. The steps of CU management were categorized into groups according to the Joint Task Force Practice Parameter (JTFPP) in CU 2014 guideline. RESULTS: One hundred children (48 males) with 'controlled CU' were recruited. The median age at first visit was 8 (5.4010.60) years. Thirty-two percent of the patients had associated angioedema. The median time to control CU was 9 (6.9011.10) months. Forty-four percent of the patients control CU with standard dose of second generation antihistamine (step 1) and the rest of the patients used the medications in step 2 to control CU. None of the patients needed systemic corticosteroid or immunomodulatory agent. The steps of treatment, angioedema and associated conditions related to CU did not affect time to control. CONCLUSIONS: Only up to a half of pediatric patients with CU had a favorable response to standard dose of second generation antihistamine. The rest required step 2 treatment of JTFPP to control their symptoms.

Efficacy of Desloratadine and Levocetirizine in Patients with Cedar Pollen-Induced Allergic Rhinitis: A Randomized, Double-Blind Study.

BACKGROUND: No comparative study of antihistamines that differ in structural system has been conducted in allergic rhinitis. OBJECTIVE: This was a randomized, double-blind, crossover comparative study to verify the efficacy of antihistamines that differ in structural system. METHODS: A total of 50 patients with moderate or more severe Japanese cedar pollen-induced allergic rhinitis were randomized to receive either placebo, desloratadine 5 mg (a tricyclic), or levocetirizine 5 mg (a piperazine). One dose of the study drug was orally administered at 9 pm on the day before a pollen exposure test, which was performed for 3 h (9 a.m. to 12 p.m.) to assess symptoms in an environmental challenge chamber (ECC). Nasal and ocular symptoms were compared at an airborne pollen level of 8,000 grains/m3. The primary endpoint was mean total nasal symptom score (TNSS) from 120 to 180 min in the ECC. Subjects with a difference of ≥1 in TNSS between 2 drugs were extracted to the relevant drug-responsive group. RESULTS: The difference in TNSS from placebo was -2.42 (p < 0.0001) with levocetirizine and -1.66 (p < 0.01) with desloratadine, showing that both drugs were significantly more effective than placebo in controlling symptoms, but with no statistically significant difference between the 2 drugs. There were 12 subjects in the desloratadine-responsive group and 24 subjects in the levocetirizine-responsive group, with no contributor to response was detected. CONCLUSION: Levocetirizine tended to control nasal symptoms more effectively than desloratadine. However, the response to each antihistamine varied among individuals and the predictors to the response are unknown. CLINICAL TRIAL REGISTRATION NUMBER: UMIN ID: UMIN000029653.

Cetirizine versus diphenhydramine in the prevention of chemotherapy-related hypersensitivity reactions.

OBJECTIVE: This study evaluated the role of cetirizine compared to diphenhydramine as premedications for patients receiving paclitaxel, cetuximab, and rituximab infusions. Historically, diphenhydramine has been linked with more sedation in comparison to cetirizine; however, it is unknown if cetirizine can replace diphenhydramine in the prevention of hypersensitivity reactions in patients receiving chemotherapy. METHODS: This is a retrospective study designed to assess infusion reactions occurring in patients receiving diphenhydramine or cetirizine premedication for rituximab, paclitaxel, or cetuximab therapies. Infusion reactions were defined as various symptoms such as flushing, itching, alterations in heart rate and blood pressure, and dyspnea plus the clinical setting of a concurrent or very recent infusion. RESULTS: A total of 207 patients were evaluated in this study with 83 patients receiving cetirizine and 124 diphenhydramine patients. Overall, the percentage of patients with at least one chemotherapy-related infusion event in the cetirizine group was 19.3% (95% CI 11.4-29.4) compared to diphenhydramine group 24.2% (95% CI 17.0-32.7), P = 0.40. Of the patients who received cetirizine and then experienced an event in the first cycle, 41.7% (95% CI 13.7-74.3) of the events were due to paclitaxel, 50.0% (95% CI 19.4-80.6) were due to rituximab, and 8.3% (95% CI 0.1-43.6) were due to cetuximab. Of the patients who received diphenhydramine and then experienced an event in the first cycle, 26.1% (95% CI 5.7-51.4) were due to paclitaxel, 73.9% (95% CI 48.6-94.3) were due to rituximab and none due to cetuximab. CONCLUSION: Cetirizine appears to be a viable substitute for diphenhydramine for the prevention of infusions reactions with cetuximab, paclitaxel, and rituximab infusions in adults. Prospective studies are needed to determine the efficacy and safety of cetirizine compared with diphenhydramine in the prevention of chemotherapy-related infusion reactions.

Antihistamines for Allergic Rhinitis Treatment from the Viewpoint of Nonsedative Properties.

Antihistamines targeting the histamine H1 receptor play an important role in improving and maintaining the quality of life of patients with allergic rhinitis. For more effective and safer use of second-generation drugs, which are recommended by various guidelines, a classification based on their detailed characteristics is necessary. Antihistamines for first-line therapy should not have central depressant/sedative activities. Sedative properties (drowsiness and impaired performance) are associated with the inhibition of central histamine neurons. Brain H1 receptor occupancy (H1RO) is a useful index shown to be correlated with indices based on clinical findings. Antihistamines are classified into non-sedating (<20%), less-sedating (20⁻50%), and sedating (≥50%) groups based on H1RO. Among the non-sedating group, fexofenadine and bilastine are classified into "non-brain-penetrating antihistamines" based on the H1RO. These two drugs have many common chemical properties. However, bilastine has more potent binding affinity to the H1 receptor, and its action tends to last longer. In well-controlled studies using objective indices, bilastine does not affect psychomotor or driving performance even at twice the usual dose (20 mg). Upon selecting antihistamines for allergic rhinitis, various situations should be taken into our consideration. This review summarizes that the non-brain-penetrating antihistamines should be chosen for the first-line therapy of mild allergic rhinitis.

C-reactive protein is linked to disease activity, impact, and response to treatment in patients with chronic spontaneous urticaria.

BACKGROUND: Elevated levels of C-reactive protein (CRP), a sensitive marker of inflammation, have been consistently reported in chronic spontaneous urticaria (CSU). Here, we retrospectively analyzed data from 1253 CSU patients from 2 centers to answer the following questions: (i) What is the prevalence of elevated levels of CRP in CSU? (ii) Why do CSU patients show elevated levels of CRP? (iii) Are elevated CRP levels relevant? METHODS: Serum levels of CRP were measured by the nephelometric method. We collected information regarding various laboratory tests including ESR, CBC with differential, D-dimer, fibrinogen, C3, C4, IL-6, etc. For most patients, we also collected data on age, gender, duration of CSU, presence of angioedema, activity (UAS at the time of blood sampling and for 7 days), quality of life (CU-Q2oL and/or DLQI), comorbidities and possible causes of CSU, and autologous serum skin test (ASST) response. The efficacy of second-generation antihistamines was evaluated on the day of blood collecting. RESULTS: One-third of CSU patients had elevated levels of CRP. Higher levels of CRP were associated with ASST positivity (P = .009) and arterial hypertension (P = .005), but not with other possible causes or comorbidities of CSU. C-reactive protein correlated with urticaria activity (P < .001), quality of life impairment (P = .026), and inflammatory and coagulation markers (P < .001). C-reactive protein levels were significantly higher in nonresponders to antihistamines as compared to responders (P < .001). CONCLUSION: Elevated levels of CRP are common and relevant in CSU patients. The assessment of CRP levels may help to optimize the management of patients with CSU.

Levocetirizine and Prednisone Are Not Superior to Levocetirizine Alone for the Treatment of Acute Urticaria: A Randomized Double-Blind Clinical Trial.

STUDY OBJECTIVE: We evaluate the efficacy of a 4-day course of prednisone added to antihistamine for the management of acute urticaria in an emergency department (ED). METHODS: In this double-blind randomized clinical trial, patients were eligible for inclusion if aged 18 years or older and with acute urticaria of no more than 24 hours' duration. Patients with anaphylaxis or who had received antihistamines or glucocorticoids during the previous 5 days were not included. In addition to levocetirizine (5 mg orally for 5 days), patients were assigned to receive prednisone (40 mg orally for 4 days) or placebo. The primary endpoint of the study was itching relief 2 days after the ED visit, rated on a numeric scale of 0 to 10. Secondary endpoints were rash resolution, relapses, and adverse events. RESULTS: A total of 100 patients were included, 50 in each group. Seven patients in the prednisone group and 8 in the placebo group discontinued treatment. At 2-day follow-up, 62% of patients in the prednisone group had an itch score of 0 versus 76% of those in the placebo group (Δ 14%; 95% confidence interval -31% to 4%). Thirty percent of patients in the prednisone group and 24% in the placebo group reported relapses (Δ 6%; 95% confidence interval -23% to 11%). Mild adverse events were reported by 12% of patients in the prednisone group and 14% in the placebo group. CONCLUSION: The addition of a prednisone burst did not improve the symptomatic and clinical response of acute urticaria to levocetirizine. This study does not support the addition of corticosteroid to H1 antihistamine as first-line treatment of acute urticaria without angioedema.

Patient-reported outcomes in urticarial vasculitis treated with omalizumab: case report.

BACKGROUND: Despite the current knowledge of UV, there is a lack of consensus among diagnostic criteria and management. In general, antihistamine therapy is regularly used for the symptomatic management of pruritus but does not control inflammation or alter the course of the disease. Monoclonal antibodies such as omalizumab (anti-IgE) have been proposed as a potential treatment for urticarial vasculitis. A few studies have reported the benefits of omalizumab in patient-reported outcome measures (PROMs). Herein we describe a female patient with urticarial vasculitis who was treated with omalizumab. We discuss the response to treatment and possible implications of PROMs in guiding the management of the disease. CASE PRESENTATION: We describe the case of a 57-year-old woman with a diagnosis of urticarial vasculitis. Due to lack of response to first-line treatment and the severity of the disease, treatment with omalizumab was initiated. Omalizumab 150 mg was administered every four weeks for three months. Second-generation antihistamines were used as needed. Both CU-Q2oL and UAS 7 improved. After three-month therapy with omalizumab, disease severity improved from moderate severity (UAS7 = 19) to well controlled (UAS7 = 6). However, 5 months after the last administration of omalizumab, the patient complained of worsening symptoms and active disease with quality of life impairment. A single dose of omalizumab (150 mg) was prescribed with corticosteroids. Thereafter, the patient presented a disease activity and quality of life with a fluctuating pattern that was controlled with additional doses of omalizumab. CONCLUSION: In chronic urticaria, patient-reported outcome measures (PROMs) are important for assessing disease status and the impact of symptoms on patients' lives. However, to our knowledge, there is no validated tool to measure such outcomes in UV patients. Although UAS7 and CU-Q2oL were not designed for UV assessment, they might be useful in the clinical setting as objective measures to determine treatment efficacy. However, some domains in the CU-Q2oL questionnaires do not correlate well with UAS7, which might serve as a relative indication to continue treatment despite disease severity improvement. Based on our observations, we believe omalizumab 150 mg might be a feasible therapeutic alternative when first-line treatment is unsuccessful.

Health care burden and treatment patterns in commercially insured children with chronic idiopathic/spontaneous urticaria: A real-world study in the United States.

BACKGROUND: Chronic idiopathic urticaria (CIU)/spontaneous urticaria (CSU) is defined by the presence of wheals, angioedema, or both for ≥6 weeks, with or without an identifiable trigger. Real-world health care data among children with CIU/CSU remain scarce. OBJECTIVES: To describe treatment patterns, health care resource utilization (HRU), and costs in pediatric patients with CIU/CSU (<12 years old) and to compare these with pediatric patients without CIU/CSU. METHODS: A commercial administrative claims data base (September 2013 to June 2016) was used. The CIU/CSU cohort included pediatric patients with either two or more claims for a diagnosis of urticaria ≥6 weeks apart or one or more claims for a diagnosis of urticaria and one or more claims for a diagnosis of angioedema ≥6 weeks apart (index was defined as the first claim). The control cohort comprised pediatric patients without urticaria or angioedema (index randomly assigned). Patients with <6 months of eligibility before and after the index date were excluded. HRU and costs were compared between the cohorts during the observation period after propensity score matching. RESULTS: A total of 6109 pediatric patients with CIU/CSU were selected, and 6107 were 1:1 matched with controls. The patients with CIU/CSU who had a mean ± standard deviation age of 4.58 ± 3.36 years, and 47.9% were girls. CIU/CSU-related medication use increased after diagnosis (e.g., baseline versus 6-month follow-up, 2.2 versus 8.0% for nonsedating prescription H1 antihistamines; 7.4 versus 17.4% for oral corticosteroids). Relative to the controls, the patients with CIU/CSU had higher rates of HRU (incidence rate ratios of 1.71, 2.39, and 2.07 for inpatient, emergency department, and outpatient visits, respectively; all p < 0.01), and higher all-cause per patient per year costs (mean cost differences of $2090, $1606, and $483 for total, medical, and pharmacy costs, respectively; all p < 0.01). CONCLUSION: This study highlighted unmet needs in pediatric patients with CIU/CSU who had increased medication (e.g., oral corticosteroids) and HRU burden after a diagnosis for CIU/CSU, and higher rates of HRU and costs relative to those without CIU/CSU.

[Severe Mast Cell Activation Syndrome in a 15-year-old patient with an hypermobile Ehlers-Danlos syndrome]. / Le cas clinique du mois. Syndrome d'Activation Mastocytaire sévère chez un patient de 15 ans présentant un syndrome d'Ehlers-Danlos de type hypermobile.

We report the history of a 15-year old patient with a hypermobile Ehlers-Danlos syndrome (hEDS) (his mother, his two brothers and his sister have the same phenotype as him). He suffers mainly from a severe mast cell activation syndrome (MCAS) with an overreaction of the skin to any kind of contact (water of the shower, clothes, bed sheets) but he has also fatigue, headaches, and rash. This impressive rash is exacerbated after the shower and he has the urge to rest («shower's sign¼). We describe the MCAS and its easy, fast and very effective medication management, without any significant side effects as well as its frequent association with the hEDS. We finally introduce the original term of «MASED¼ to this MCAS, associated, linked or entangled to hEDS.

Nous présentons le cas d'un jeune patient âgé de 15 ans atteint d'un syndrome d'Ehlers-Danlos (SED) de type hypermobile (sa mère, ses deux frères et sa soeur présentent le même phénotype que lui). Il présente principalement un syndrome d'activation mastocytaire (SAMA) sévère avec une atteinte démesurée au niveau de la peau exposée au simple contact (avec l'eau, les draps, les vêtements), mais également de la fatigue, des céphalées ainsi que des éruptions qui sont exacerbées après la douche avec l'envie impérieuse de se reposer (le «signe de la douche¼). Nous décrivons le SAMA, sa prise en charge médicamenteuse simple, rapide et efficace et dépourvue d'effets secondaires notables ainsi que son association fréquente au SED. Nous introduisons finalement le terme original de «SAMED¼ à ce SAMA associé, lié ou intriqué au SED.

[Association of CACNA1C gene genetic polymorphism with the susceptibility as well as prognosis for chronic spontaneous urticaria].

OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of CACNA1C (SNPs rs58619945, rs7316246 and rs216008) and susceptibility of chronic spontaneous urticaria (CSU) as well as the curative effect of non-sedating antihistamine drugs.
 Methods: Peripheral blood were extracted from 191 CSU patients to collect DNA. Urticaria Activity Score 7 (UAS7) and Dermatology Life Quality Index (DLQI) changes were collected from these patients with different non-sedating antihistamine drugs. PubMed retrieval system was used to select the 3 SNPs (rs58619945, rs7316246 and rs216008) of CACNA1C. Susceptibility of CSU and curative effect of non-sedating antihistamine drugs (desloratadine, mizolastine, fisofenadine) in 189 CSU patients and 105 controls with different SNPs were compared with Chi-squared test. Data of 105 southern Chinese controls were extracted from the 1 000 genome database.
 Results: Frequency of rs58619945 G allele in the CSU patients was significantly higher than that in the controls [OR(95%CI)=0.660(0.470-0.925), P=0.016]. However, there was no significant differences in rs7316246 and rs216008 between the CSU patients and the controls. Meanwhile there was no significant difference in general curative effect of the 3 drugs in the 3 SNPs (rs58619945: OR=0.843, P=0.454; rs7316246: OR=2.103, P=0.102; rs216008: OR=0.237, P=0.363). There was significant difference in different alleles of rs216008 in the patients administered by desloratadine [OR(95%CI)=0.480(0.247-0.933), P=0.029]. No difference was shown in the 3 SNPs in patients administered by mizolastine.
 Conclusion: The rs58619945 A/G might be related to susceptibility of CSU, and the rs216008 mutation might affect drug response of desloratadine.

Effectiveness of Autologous Whole-Blood Injections in Patients with Refractory Chronic Spontaneous Urticaria.

BACKGROUND: Nonsedating antihistamines are the treatment of choice for chronic spontaneous urticaria (CSU), while omalizumab and immunosuppressants have also been approved as an add-on treatment. Autologous whole-blood injection (AWBI) has been used in previous studies with ambiguous results. The aim of our study was to evaluate changes in the Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and Chronic Urticaria Quality of Life (CU-Q2oL) score, and also the association of serologic markers with disease severity measures after AWBI. METHODS: In this observational study, AWBIs were performed (8 courses on a weekly basis) in adults with refractory CSU, who refused an add-on treatment with either omalizumab or immunosuppressants. UAS7, DLQI, and CU-Q2oL questionnaires and serum concentrations of total IgE, C-reactive protein (CRP), and D-dimer were evaluated before and after the intervention. RESULTS: Nineteen patients (12 females; mean age 54 ± 20.8 years) completed the protocol. Following AWBI, significant improvements in the UAS7 (34.26 ± 8.04 vs. 12.52 ± 10.83, p < 0.001), DLQI (11.63 ± 5.51 vs. 3.47 ± 2.85, p < 0.001), and CU-Q2oL score (32.97 ± 18.71 vs. 10.94 ± 7.71, p < 0.001) were recorded. A negative correlation between the baseline D-dimer levels and UAS7 and DLQI variations (p = 0.002 and p = 0.001, respectively) was noted. D-dimer levels ≥292 ng/mL have been associated with poor responsiveness (sensitivity 75%; specificity 83.3%). No correlation with either total immunoglobulin E or CRP levels was observed. CONCLUSION: AWBI appears to be a safe, alternative, add-on therapeutic option in refractory CSU, particularly in patients with low plasma levels of D-dimer.