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Background and objectives Atopic dermatitis is a chronic inflammatory skin disease with a prevalence of 0.02% to 8.1% in adults. Adult patients with moderate-to-severe atopic dermatitis have frequent relapses and significant disease burden. Objectives: Characterize clinical, immunological and therapeutic features of Brazilian adults with atopic dermatitis. Methods A multicenter, observational, retrospective, descriptive registry-based study, conducted at reference hospitals, between December 2016 and October 2017. Demographics, personal and family history of atopic diseases, clinical manifestations, laboratory tests, disease severity and management were collected. Results From the 187 subjects included in the analysis, 56.1% were female and 71.7% were Caucasian, with a mean age of 24.7 years. Mean follow-up duration was 9 years. Asthma or other allergic diseases were reported by 80.2% of the patients. The main comorbidity was hypertension (10.2%) and common disease manifestations included pruritus and erythema. Lesions were generally distributed in non-flexural and flexural areas, with typical morphology. Around 83% of patients had moderate to severe disease and 8.6% reported at least one hospitalization. Most patients received topical and/or systemic pharmacological therapies, including omalizumab (5.9%); 4.3% received phototherapy. Moreover, 66.8% of patients received adjuvant therapy and 79.1% changed or discontinued treatment for atopic dermatitis due to remission (46.5%), poor effectiveness (33.7%) or lack of therapeutic adherence (12.9%). Most patients presented characteristics of type 2 inflammation, with immunoglobulin E levels above 100 IU/mL (94.4%) and peripheral blood eosinophils above 5% (55.9%). Conclusion Brazilian adult patients with severe atopic dermatitis need treatments to efficiently control the disease and improve quality of life.

Background Sensitization to house dust mites (HDM) is frequent in patients with atopic dermatitis (AD). Objective To investigate the efficacy of sublingual immunotherapy (SLIT) with Dermatophagoides pteronyssinus(Dpt) extract in patients with AD sensitized to HDM. Methods In this randomized, double-blind, placebo-controlled trial, we enrolled 91 patients aged ≥3 years, with SCORing Atopic Dermatitis (SCORAD) ≥15 and positive skin test and/or IgE to Dpt. Patients were stratified according to age ( > 15-point decrease in SCORAD. Secondary outcomes were decreases in SCORAD and objective SCORAD (O-SCORAD), Eczema Area and Severity Index (EASI), visual analog scale (VAS) for symptoms, pruritus scale; Investigator’s Global Assessment (IGA) 0/1; and decrease ≥4 points in Dermatology Life Quality Index (DLQI). Background therapy was maintained. Results A total of 66 patients completed the study (35 HDM SLIT, 31 placebo). After 18 months, 74.2% and 58% patients in HDM SLIT and placebo groups, respectively, showed > 15-point decrease in SCORAD (relative risk[RR]1.28, 95% confidence interval[CI] 0.89-1.83). Significant SCORAD decreases from baseline of 55.6% and 34.5% in HDM SLIT and placebo groups (mean difference 20.4;95%CI 3.89-37.3); significant O-SCORAD decreases of 56.8% and 34.9% in HDM SLIT and placebo groups (mean difference 21.3;95%CI 0.66-41.81); and more patients with IGA 0/1 in HDM SLIT group as compared to placebo group (14/35 vs 5/31;RR 2.63, 95%CI 1.09-6.39), were observed at 18 months. Conclusion Our results suggest that HDM SLIT may be effective in HDM sensitized patients as an add-on treatment for AD.

Angioedema attacks are common causes of emergency care, and due to the potential for severity, it is important that professionals who work in these services know their causes and management. The mechanisms involved in angioedema without urticaria may be histamine- or bradykinin-mediated. The most common causes of histamine-mediated angioedema are foods, medications, insect sting and idiopathic. When the mediator is bradykinin, the triggers are angiotensin-converting enzyme inhibitors and factors related to acquired angioedema with deficiency of C1-inhibitor or hereditary angioedema, which are less common, but very important because of the possibility of fatal outcome. Hereditary angioedema is a rare disease characterized by attacks of edema that affect the subcutaneous tissue and mucous membranes of various organs, manifesting mainly by angioedema and abdominal pain. This type of angioedema does not respond to the usual treatment with epinephrine, antihistamines and corticosteroids. Thus, if not identified and treated appropriately, these patients have an estimated risk of mortality from laryngeal edema of 25% to 40%. Hereditary angioedema treatment has changed dramatically in recent years with the development of new and efficient drugs for attack management: plasma-derived C1 inhibitor, recombinant human C1-inhibitor, bradykinin B2 receptor antagonist (icatibant), and the kallikrein inhibitor (ecallantide). In Brazil, plasma-derived C1 inhibitor and icatibant have already been approved for use. Proper management of these patients in the emergency department avoids unnecessary surgery and, especially, fatal outcomes.

Introduction: Hereditary angioedema (HAE) with C1 inhibitor (C1-INH) deficiency is a rare autosomal dominant disease. Although the first symptoms can appear in childhood, the diagnosis’s delay has a strong impact on the patient’s quality of life. We analyzed clinical and laboratory characteristics and the drug therapy of pediatric patients with HAE in Brazil. Methods: Medical records from 18 reference centers of HAE patients under 18 years of age were evaluated after confirmed diagnosis was performed by quantitative and/or functional C1-INH. Results: A total of 95 participants (51 M:44 F; mean age: 7 years old) out of 17 centers were included; 15 asymptomatic cases were identified through family history and genetic screening. Angioedema attacks affected the extremities (73.5%), gastrointestinal tract (57%), face (50%), lips (42.5%), eyelids (23.7%), genitals (23.7%), upper airways (10%), and tongue (6.3%). Family history was present in 84% of patients, and the mean delay in the diagnosis was 3.9 years. Long-term prophylaxis (51/80) was performed with tranexamic acid (39/80) and androgens (13/80); and short-term prophylaxis (9/80) was performed with tranexamic acid (6/80) and danazol (3/80). On-demand therapy (35/80) was prescribed: icatibant in 7/35, fresh frozen plasma in 16/35, C1-INH plasma-derived in 11/35, and tranexamic acid in 12/35 patients. Conclusions: This is the first study on HAE pediatric patients in Latin America. Clinical manifestations were similar to adults. Drugs such as androgens and tranexamic acid were indicated off-label, probably due to restricted access to specific drugs. Educational programs should address pediatricians to reduce late diagnosis and tailored child therapy.

Introduction: Patients with severe asthma may present with different phenotypes. Severe eosinophilic asthma patients require frequent use of health care resources and have impaired health-related quality of life. Objective: We sought to determine the prevalence of an eosinophilic phenotype, defined as blood eosinophil counts >300 cells/mm3, for patients with severe asthma in Brazil. Methods: This was a cross-sectional, observational study of adult patients with severe asthma (high dose inhaled corticosteroid [GINA 2018] plus second controller) in routine clinical practice in Brazil. Allergic phenotype was defined as serum IgE>100 IU/mL plus clinical features of allergy. Results: A total of 385 patients were enrolled from 10 Brazilian centers. Most were female (78.4%) and white (57.4%), with a mean age of 53±13 years old. Prevalence of patients with eosinophilic phenotype was 40.0% [95% CI: 35.1–44.9%]. Those were mainly female (76.0%), white (62.3%), with mean age 50±14 years old. Eosinophilic patients presented lower BMI, with no other relevant clinical or demographics differences compared with non-eosinophilic phenotype patients. A high prevalence of allergic phenotype of 62.6% [95% CI: 57.8%-67.4%] was also identified. There was a high overlap between phenotypes as 79.9% [95% CI: 73.5–86.2%] of eosinophilic patients were also allergic. Conclusions: The prevalence of an eosinophilic phenotype for patients with severe asthma in Brazil is high, and these patients present with clinical and demographic characteristics similar to other worldwide populations. The overlap between allergic and eosinophilic phenotypes was common.

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 experience of the GA2LEN UCARE network and (b) input from angioedema patients, general practitioners, and angioedema specialists.

SummaryBackground Workers exposed to laboratory animals have a high risk of developing laboratory animal allergy (LAA). Atopy seems to be the main risk factor for LAA. We hypothesized that occupational sensitization is a better predictor for the development of asthma, rhinitis, and bronchial hyperresponsiveness (BHR) than common sensitization. Objective To investigate the association between occupational sensitization to laboratory animals and clinical outcomes. Methods This was a cross-sectional study performed at two universities on students and employees dealing with small rodents. The subjects were allocated in groups: non-sensitized, common sensitization, or occupational sensitization, according to the results of the skin prick test (SPT). All subjects answered a questionnaire about animal exposures, symptoms, allergic diseases, and underwent spirometry and bronchial challenge test with mannitol. Multivariate analysis was performed using Poisson regression to estimate the prevalence ratio (PR). Results Data from 453 volunteers were analysed. Non-sensitized group comprised 237 subjects; common sensitization group, 142 subjects; and occupational sensitization group, 74 subjects. Occupational sensitization was associated with greater risk for all outcomes studied. When the common sensitization group was reference, skin symptoms had PR of 1.36, 95% confidence interval (CI): 1.01-1.85; wheezing had PR of 1.75, CI 95%: 1.21-2.53; rhinitis had PR of 1.25, 95%: 1.11-1.40; nocturnal dyspnoea had PR of 2.40, 95% CI: 1.31-4.40; bronchial hyperresponsiveness (BHR) had PR of 2.47, 95% CI: 1.50-4.09; and confirmed asthma had PR of 2.65, 95% CI: 1.45-4.85. In addition, the overlap of asthma, rhinitis, and skin symptoms in a same subject was significantly more prevalent in the occupational sensitization group, 16.2% versus 4.9% in the common sensitization group. Conclusion and Clinical Relevance Occupational sensitization is associated with allergic symptoms and respiratory diseases. SPT with occupational allergens along with other parameters may contribute to detection of risk for allergic and respiratory diseases associated with exposure to laboratory animals.

Background Factors associated with recurrence of chronic rhinosinusitis (CRS) are still poorly recognized. Objective To evaluate which risk factors could influence the risk of recurrence among patients undergoing endoscopic sinus surgery in long-term follow-up. Methods Patients with CRS who underwent endoscopic sinus surgery were followed for an average period of 12 years in a nonconcurrent cohort. After surgery, patients were considered to an additional endoscopic sinus surgery if appropriate medical therapy failed during this period. The presence of nasal polyps, asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, smoking habits, peripheral blood eosinophilia, and atopy were assessed. The recurrence-free interval between groups (with or without these risk factors) was analyzed by Kaplan-Meyer curves, and the indication for a revisional surgery was considered to be the unfavorable event. Results A total of 201 patients were enrolled in this study. Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) were more likely than patients with chronic rhinosinusitis without nasal polyps (CRSsNP) to need revisional surgery (adjusted hazard ratio, 2.02). Asthma was the only factor that was significantly related to recurrence both in patients with CRSsNP (hazard ratio, 5.54) and in patients with CRSwNP (hazard ratio, 3.27). Although eosinophilia itself was not related to a higher chance of recurrence, its presence influenced the outcome of CRSwNP compared with CRSsNP and the impact of asthma among patients with CRSwNP. Conclusions Prognosis in patients with CRSwNP was inferior to that in patients with CRSsNP. Asthma was the only factor that increased the chance of recurrence in patients with either CRSsNP or CRSwNP.

Background: Anaphylaxis is a severe and potentially fatal allergic disease or hypersensitivity reaction with variable clinical presentation. Biomarkers in anaphylaxis could be useful to improve diagnosis, to allow endotyping of patients, and to predict risk. Objective: To investigate the role of serum basal tryptase (sBT) levels in the management of patients with anaphylaxis. Methods: Patients with at least 1 episode of anaphylaxis were selected among those who attended the Allergy Clinics of the Clinical Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil, upon evaluation by allergy/immunology specialists of our medical staff. Demographic and clinical data were obtained using a structured questionnaire. sBT levels were determined using the ImmunoCAP Tryptase immunoassay. Results: 57 patients (56.1% female) with a median age of 35 years (range 7–87 years) participated in the study. sBT levels ranged from 2.57 to 21.19 ng/mL (mean 5.17 ng/mL), with no significant differences in patients with anaphylaxis due to different triggers. Mean levels were 4.93; 5.2; 5.41, and 5.24 ng/mL for patients who had anaphylaxis due to Hymenoptera venom (n = 17), foods (n = 13), drugs (n = 13), and idiopathic disease (n = 14), respectively. Significantly higher sBT levels were observed in patients with severe anaphylaxis (grade IV) than in patients with mild-moderate disease (grades II/III) (mean levels 6.61 vs. 4.71 ng/mL, respectively). Conclusion: High sBT levels may help to identify patients at increased risk of more severe anaphylaxis, prompting physicians to initiate immediate therapy to avoid further acute episodes.

Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the “Associação Brasileira de Alergia e Imunologia (ASBAI)” and the “Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)” has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

The subspecialty of pediatric allergy and immunology in Brazil is in its early years and progressing steadily. This review highlights the research developed in the past years aiming to show the characteristics of allergic and immunologic diseases in this vast country. Epidemiologic studies demonstrated the high prevalence of asthma in infants, children, and adolescents. Mortality rates and average annual variation of asthma hospitalization have reduced in all pediatric age groups. Indoor aeroallergen exposure is excessively high and contributes to the high rates of allergy sensitization. Prevalence of food allergy has increased to epidemic levels. Foods (35%), insect stings (30%), and drugs (23%) are the main etiological agents of anaphylaxis in children and adolescents. Molecular diagnosis of primary immunodeficiencies (PID) showed a high incidence of fungal infections including paracoccidioidomycosis in X-linked hyper-IgM syndrome, and the occurrence of BCG adverse reactions or other mycobacterial infections in patients with chronic granulomatous disease. Education in pediatric allergy and immunology is deficient for medical students, but residency programs are effective in training internists and pediatricians for the practice of allergy. The field of PID requires further training. Last, this review is a tribute to Prof. Dr. Charles Naspitz, one of the pioneers of our specialty in Brazil.

Objectives To evaluate the sensitization to aeroallergens determined by skin prick test (SPT) in Brazilian adolescents, and to correlate its positivity with the diagnosis of asthma and/or rhinitis based on the written questionnaire (WQ) of ISAAC phase III study. Patients and Methods A total of 996 adolescents (387 boys) were selected by systematic samples. A standard allergen extracts panel (positive/negative control, D pteronyssinus [Dpt], P americana [Pa], B germanica [Bg], dog, cat, fungal and grass mix) was used and its positivity compared with positive responses to asthma, rhinitis or both. Results Positive SPT to at least one allergen was observed in 466 adolescents (46.8 %), with sensitization to Dpt in 79.1 %. Positivity to more than one allergen occurred in 232 students (49.8 %). The frequency of positive SPTs was significantly higher among adolescents with asthma (OR = 2.16), rhinitis (OR = 1.69), and asthma and rhinitis (OR = 2.03). Positive SPT to four or more allergens were higher among asthmatics (OR = 2.6) and among adolescents with asthma and rhinitis (OR = 3). Conclusions A high sensitisation rate to aeroallergens was observed, significantly higher among those with asthma, rhinitis or a combination of both, especially in multiple sensitisations.

Background: Current guidelines on chronic spontaneous urticaria (CSU) suggest a treatment based on a 3-step approach that aims at total symptom control, starting with H1-antihistamines. However, a significant number of patients present an antihistamine-resistant urticaria that must be treated with an alternative third-line therapy such as omalizumab. Methods: Patients with a history of CSU who did not respond to treatment with high doses of modern antihistamines were treated with 150 or 300 mg of omalizumab every 4 weeks. The response to treatment was recorded as complete (CR), partial (PR) or no response. A dose adjustment was proposed according to response. Results: We treated 47 CSU patients with omalizumab (40 females), of whom 39.5% had evidence of autoimmunity. The average number of treatments was 11.4 (range 2-87). All patients had been refractory to high-dose modern antihistamines. A CR was seen in 84.6% of patients who started with 300 mg and in 60% of those who started with 150 mg. Only 1 patient had no response to both the 150- and 300-mg doses. In 6 of the PR patients with 150 mg, a higher dose of 300 mg was proposed and 4 had a CR. Four patients discontinued the treatment. No severe adverse events were reported in the patients who finished the study. Discussion: Although good results were seen in both groups, CR rates were higher in those under a high-dose initial treatment. Our data strongly suggest that the therapy should be individualized.

Written questionnaires (WQ) have been widely used in epidemiologic studies. In order to yield comparable results, they must be validated after translation to another language. The International Study of Asthma and Allergies in Childhood (ISAAC) WQ has been previously validated by a comprehensive study, but its validation in Brazil has not been performed. Our objectives were to validate the rhinitis component of the ISAAC's self-applicable WQ following its translation to Portuguese, and to determine the prevalence of rhinitis and related symptoms among Brazilian children living in the city of Sao Paulo. A group of 10 pediatricians and 10 pediatric allergists graded the questions from 0 to 2 and established a maximum score for each question. The WQ was answered by parents or guardians of children 6-7 years of age with rhinitis (R) (n = 27) and of control children of the same age without rhinitis (C) (n = 27). The WQ was also completed by adolescents 13-14 years of age with rhinitis (R) (n = 32) and without rhinitis (C) (n = 32). Half of these individuals answered the same WQ after 2-4 weeks, to ensure reproducibility. Cut-off scores of 4 and 3 were identified for the 6-7- and 13-14-year-old groups, respectively, as scores predictive of rhinitis. The prevalence of rhinitis was 28.8% in the group of 3005 children 6-7 years of age and 31.7% in the group of 3008 children 13-14 years of age, respectively. Using the global cut-off score, these prevalences were even higher, in the order of 34.7% and 40.7%, respectively. In conclusion, the rhinitis component of the ISAAC WQ was proven to be reproducible, adequate and able to discriminate children and adolescents with and without rhinitis, and revealed that the prevalence of rhinitis among Brazilian children living in the city of Sao Paulo was as high as the prevalence of rhinitis in other areas of the world.

Methods Prospective study including 116 patients with positive history of hypersensitivity to NSAIDs, evaluated at the Allergy Clinic of the Clinical Hospital of Ribeirao Preto Medical School, between October 2010 and July 2014. Patients were evaluated using the European Network for Drug Allergy questionnaire, and underwent single blind, placebo controlled OCT, in a hospital-controlled environment. Patients were required to be clinically stable, and to withdraw antihistamines or corticosteroids seven days prior to the OCT. Patients were given 10%, 20%, 30% and 40% of the therapeutic NSAID dosage, selecting an NSAID different from the one implicated in the allergic reaction. Fifteen minutes after each dosage, patients were evaluated with Peak Flow and blood pressure measurements, heart and respiratory rates and general examination.

Rationale The aim of this study was to investigate the role of autoimmunity in children and adolescents with chronic urticaria. Methods We have studied 38 children aged 2 to 17 years-old (20 females), who were referred to the allergy clinic for evaluation of chronic urticaria in the preceding 4 years. Age at onset of symptoms varied from 6 months to 15 years (mean 5.3 years), duration of symptoms ranged from 6 weeks to 10 years (mean 2.4 years), and 63% patients also presented angioedema. Each patient underwent clinical evaluation, skin prick testing with inhalant and food allergens, and blood testing including detection of anti-nuclear antibodies, antithyroid antibodies, thyroxine and TSH levels and measurements of total IgE and specific IgE antibodies (Pharmacia CAP system). Autologous skin testing was carried out in 28/38 patients. Results Positive skin tests and/or serum IgE antibodies (CAP score ≥2) to inhalant and food allergens were detected in 65% and 76% of patients, respectively. Associated conditions were (number of patients): allergic rhinitis (14), asthma (5), precocious puberty (2), atopic dermatitis, JRA and anaphylaxis to insect sting (1 each). Evidence for autoimmunity was present in a subset of children: 15/28 (53%) had a positive autologous skin test and 3/30 had positive ANA (≥1:20). Two patients had elevated TSH (>4 mIU/L) with normal thyroxine levels, and no patient had detectable (≥35 IU/mL) antithyroid peroxidase antibodies. Conclusion An autoimmune mechanism may underlie the pathogenesis of chronic urticaria in a subset of children with this condition.

Rationale We have evaluated risk factors associated with persistence of wheezing beyond the first two years of life among children living in a subtropical area. Methods 80 children who had been seen at the Emergency Room for an episode of wheezing in the first 2 years of life were followed for 2 years in this prospective study. Children underwent clinical evaluation and skin prick testing to inhalant and food allergens two years following the index episode of wheezing. Detection of respiratory viruses and analysis of house dust samples for exposure to major allergens from mites, cockroach, cat and dog (by ELISA) were carried out at enrollment. Total IgE and specific IgE antibodies (Pharmacia CAP system) were measured at the beginning of the study and at the end of follow-up. Multivariate analysis was performed to identify factors associated with persistent wheezing. Results 73 children (44 boys) completed the study. After 2 years, 38 (52%) presented 3 or more wheezing episodes treated with beta-2 agonists in the past 12 months (persistent wheezers). Risk factors for persistence of wheezing were: family history of allergy (OR=48.6; p=0.03), exposure to levels of cockroach allergen Bla g 1 >2U/g in the kitchen (OR=7.6; p=0.03) and allergic sensitization at age 2-4 (OR=11.3; p=0.002). Breast-feeding for at least one month was a protective factor (OR=0.08; p=0.01). Conclusions Environmental exposure to high levels of cockroach allergen in infancy, sensitization to indoor allergens at age 2-4 and family history of allergy were strongly and independently associated with persistent wheezing in children.