Solange Oliveira Rodrigues Valle

Hereditary angioedema: quality of life in Brazilian patients

OBJECTIVE: Hereditary angioedema is a serious medical condition caused by a rare autosomal dominant genetic disorder and it is associated with deficient production or dysfunction of the C1 esterase inhibitor. In most cases, affected patients experience unexpected and recurrent crises of subcutaneous, gastrointestinal and laryngeal edema. The unpredictability, intensity and other factors associated with the disease impact the quality of life of hereditary angioedema patients. We evaluated the quality of life in Brazilian hereditary angioedema patients. METHODS: Patients older than 15 years with any severity of hereditary angioedema and laboratory confirmation of C1 inhibitor deficiency were included. Two questionnaires were used: a clinical questionnaire and the SF-36 (a generic questionnaire). This protocol was approved by the Ethics Committee of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTS: The SF-36 showed that 90.4% (mean) of all the patients had a score below 70 and 9.6% had scores equal to or higher than 70. The scores of the eight dimensions ranged from 51.03 to 75.95; vitality and social aspects were more affected than other arenas. The internal consistency of the evaluation was demonstrated by a Cronbachs alpha value above 0.7 in seven of the eight domains. CONCLUSIONS: In this study, Brazilian patients demonstrated an impaired quality of life, as measured by the SF-36. The most affected domains were those related to vitality and social characteristics. The generic SF-36 questionnaire was relevant to the evaluation of quality of life; however, there is a need for more specific instruments for better evaluation.

Cross‐cultural adaptation of the Brazilian–Portuguese version of the chronic urticaria quality‐of‐life questionnaire – CU‐Q2oL

To cite this article: Dias GAC, Pires GV, Valle SOR, França AT, Papi JA, Dortas SD Jr, Levy SAP, Baiardini I, Canonica GW. Cross‐cultural adaptation of the Brazilian‐Portuguese version of the chronic urticaria quality‐of‐life questionnaire ‐ CU‐Q2oL. Allergy 2011; 66: 1487–1493

Validity and Reproducibility of the Asthma Core International Study of Asthma and Allergies in Childhood (ISAAC) Written Questionnaire Obtained by Telephone Survey

Objective. To assess the reproducibility and validity of the International Study of Asthma and Allergies in Childhood (ISAAC) asthma written questionnaire (IAWQ) for 6- to 7-year-old children administered to their parents/caregivers through a telephone interview. Methods. Our study included 100 children selected from three health units in Rio de Janeiro, Brazil. In total, 50 asthmatic and 50 non-asthmatic children were evaluated; all participants were required to own a household telephone line. Initially, telephone interviews were conducted with the parents/caregivers using the IAWQ. After 2 weeks, parents/caregivers were invited to complete the IAWQ under supervision provided by the researchers. After fifteen days, the telephone interviews were repeated. The reproducibility between the two telephone interviews was assessed using kappa (κ) coefficients; the construct validity was assessed by comparing the answers obtained in the initial telephone interview in both groups according to the clinical diagnosis of asthma performed by a specialist using sensitivity and specificity coefficients. Results. Overall, data from 75 children (39 asthmatics) were analyzed, as 25 patients were excluded from the study (11 did not answer phone calls and the responding parents/caregivers for 14 patients were not the same in all study phases). Perfect agreement was observed for the indicator “wheezing in the last 12 months” (κ = 1), while substantial agreement was observed for the “wheezing with exercise,” “speech limited by wheezing,” and “asthma ever” indicators (κ range, 0.7–0.8). The sensitivity and specificity for “wheezing within the last 12 months” were 64.1% (95% confidence interval (CI), 47.2–78.8) and 88.9% (95% CI, 73.9–96.9), respectively. For the “asthma ever” indicator, the sensitivity and specificity were 87.2% (95% CI, 77.6–95.7) and 100% (95% CI, 90.3–1), respectively. Questionnaire specificity was high for all asthma severity indicators. Conclusions. The IAWQ for children aged 6–7 years adapted for telephone interviews showed good reproducibility and adequate validity with an ability to distinguish between asthmatic and non-asthmatic participants. Thus, this method could be utilized in epidemiological studies on childhood asthma in locations where telephone lines are available.

Brazilian guidelines for the diagnosis and treatment of hereditary angioedema

Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom the disease goes undetected and who are therefore incorrectly treated is 25-40%. In addition to edema of the glottis, hereditary angioedema often results in edema of the gastrointestinal tract, which can be incapacitating. Patients with hereditary angioedema may undergo unnecessary surgical interventions because the digestive tract can be the primary or only organ system involved, thus mimicking acute surgical abdomen. It is estimated that patients with hereditary angioedema experience some degree of disability 20-100 days per year. The Experts in Clinical Immunology and Allergy of the “Associação Brasileira de Alergia e Imunopatologia - ASBAI” developed these guidelines for the diagnosis, therapy, and management of hereditary angioedema.

Omalizumab in Chronic Spontaneous Urticaria: A Brazilian Real-Life Experience

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.

Atopy patch test (APT) in the diagnosis of food allergy in children with atopic dermatitis

BACKGROUND Atopic Dermatitis is a chronic inflammatory skin disease. Food allergens are important in the pathogenesis in 1/3 of the cases. Several mechanisms are involved in the pathogenesis of Atopic Dermatitis. Immediate reactions are identified by both measurement of specific IgE and skin prick test. Atopy Patch Test seems to be relevant in the investigation of patients with suspected delayed-type reactions. OBJECTIVES To evaluate the standardization of this method concerning allergen concentration, occlusion time and interpretation, and determine the specificity and sensitivity of the Atopy Patch Test according to the skin prick test and specific IgE levels in food allergy diagnosis in children with Atopic Dermatitis. METHODS Seventy-two children, aged 2-12 years were selected and followed at the allergy clinic of the Hospital São Zacharias. Skin prick test, specific IgE and food Atopy Patch Test (cows milk, egg, soy and wheat) were carried out. Three groups were submitted to the Atopy Patch Test: (1) Atopic Dermatitis with or without Rhinitis and Asthma; (2) Rhinitis and or Asthma without AD; (3) Healthy individuals. RESULTS In group 1, 40% of the patients presented positive reactions. The longer the exposure time (48h and 72h), the higher the sensitivity. In group 2, the test was more specific than sensitive for all the extracts, with increased sensitivity the longer the time of exposure (72h). In group 3, 8.3% presented positive tests. CONCLUSION APT evidenced a great diagnostic value in late-phase reactions to food, with high specificity. It showed to be a specific and reliable tool in comparison with the healthy groups results.FUNDAMENTOS: A Dermatite Atopica e uma doenca inflamatoria cronica da pele. Os alimentos sao importantes na patogenese da doenca em 1/3 dos casos. Diversos mecanismos estao envolvidos na fisiopatogenia da dermatite Atopica. As reacoes imediatas sao identificadas pela dosagem de IgE especifica e teste de puntura. O teste de contato atopico parece ter relevância na investigacao de pacientes com suspeita de reacao tardia. OBJETIVOS: Avaliar a padronizacao do metodo com relacao a concentracao do alergeno, tempo de oclusao e de interpretacao; e determinar a especificidade e a sensibilidade do teste de contato atopico em relacao ao teste de puntura e a dosagem de IgE especifica, no diagnostico de alergia alimentar em criancas com dermatite Atopica. METODOS: Setenta e duas criancas com 2 a 12 anos foram submetidas a teste de puntura e dosagem de IgE especificas para alimentos (leite de vaca, ovo, soja, trigo). O teste de contato atopico foi aplicado em 3 grupos: (1) Dermatite Atopica com ou sem Rinite e Asma; (2) Rinite e ou Asma sem Dermatite Atopica; (3) Saudaveis. RESULTADOS: No grupo 1, 40% dos pacientes apresentaram reacao positiva. Quanto maior o tempo de exposicao, maior foi a sensibilidade. No grupo 2, o teste foi mais especifico que sensivel para todos os extratos; com aumento da sensibilidade com maior tempo de exposicao (72h). No grupo 3, 8.3% apresentaram testes positivos. CONCLUSAO: O teste de contato atopico mostrou ter valor diagnostico em relacao as reacoes de fase tardia a alimentos, com elevada especificidade. Mostrou-se um teste especifico e confiavel ao comparar com os resultados do grupo controle.

Coagulation Factor XII Gene Mutation in Brazilian Families with Hereditary Angioedema with Normal C1 Inhibitor

Background: Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) is a rare disorder. Mutations of the gene encoding coagulation factor XII have been identified in a subset of patients with this condition. Our aim was to investigate mutations in the F12 gene in patients with HAE with normal C1-INH from Brazil. Methods: We studied 5 Brazilian families with index female patients who presented with recurrent angioedema with normal C1-INH and C4 levels. Genomic DNA was isolated from whole blood and PCR was performed. Mutations were detected by the sequencing of exon 9 of the F12 gene and allelic discrimination. Results: The c.983C>A (p.Thr328Lys) mutation was identified in 16 subjects, from 4 of the 5 families studied, including 8 patients with symptoms of HAE with normal C1-INH (87.5% women) and 8 subjects asymptomatic for HAE (25% women). Mean age at onset of symptoms among the FXII-HAE patients was 13.8 years (range 6-25 years). Recurrent abdominal pain (100%) and subcutaneous angioedema (87.5%) were the most frequent clinical presentations. Two patients presented with associated laryngeal edema. In keeping with previous observations in patients with both C1-INH-HAE and HAE with normal C1-INH, all 7 women with FXII-HAE reported triggering or worsening of symptoms upon intake of estrogen-containing oral contraceptives and/or pregnancy. Conclusions: We report for the first time in Brazil a mutation in the F12 gene as a likely cause of HAE with normal C1-INH in patients with recurrent attacks of angioedema and/or abdominal pain. A higher frequency of abdominal pain attacks and onset of symptoms at a younger age were observed among Brazilian patients when compared to those from other parts of the world.

Frequency of viral etiology in symptomatic adult upper respiratory tract infections

Abstract Aims To determine the frequency of viral pathogens causing upper respiratory tract infections in non-hospitalized, symptomatic adults in the city of Rio de Janeiro. Methods Respiratory samples (nasal/throat swabs) were collected between August 2010 and November 2012 and real time PCR was used to detect different viral pathogens. Results Viruses were detected in 32.1% (43/134) of samples from 101 patients. Specifically, 9% (12/134) were positive for HBoV, 8.2% (11/134) were positive for HAdV, 5.2% (7/134) were positive for HRV, and 1.5% (2/134) were positive for FLUBV or HMPV, as single infections. HRSV-A, HPIV-3, and HCoV-HKU1 were detected in one (0.75%) sample each. Co-infections were detected in 4.8% (6/134) of the samples. Peaks of viral infections were observed in March, April, May, August, and October. However, positive samples were detected all year round. Only 23.3% (10/43) of the positive samples were collected from patients with febrile illness. Conclusion Results presented in this report suggest that respiratory viral infections are largely under diagnosed in immunocompetent adults. Although the majority of young adult infections are not life-threatening they may impose a significant burden, especially in developing countries since these individuals represent a large fraction of the working force.

Urticária de pressão tardia com manifestações sistêmicas: relato de caso

Delayed Pressure Urticaria is considered a rare disease,with clinical diagnosis different from classical urticaria, with possible systemic manifestations. Therefore, it is Frequently underdiagnosed, even by specialists. In this article, the case of a patient with a typical history of pressure-induced lesions is presented. Because the patient had fever and leukocytosis, she was admitted to a hospital for investigation of infection.

Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective experimental single-cohort study

CONTEXT AND OBJECTIVE Hereditary angioedema (HAE) with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil. DESIGN AND SETTING Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients. METHODS Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored. RESULTS 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age). The symptoms were: subcutaneous edema (22/24); abdominal pain (15/24) and upper airway obstruction (10/24). The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%); 10-20 (5/24; 20.8%); 20-30 (8/24; 33.4%); 30-60 (5/24; 20.8%); and 2 hours (1/24; 4.3%). The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6. CONCLUSION HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.