Hereditary angioedema: Screening of first-degree blood relatives and earlier diagnosis.

Background: Hereditary angioedema (HAE) with C1 inhibitor (C1INH) deficiency is an inherited disease characterized by sudden, recurrent episodes of edema that involve the skin, gastrointestinal tract, respiratory tract, and other organs. Objective: Because it takes a long time from the first symptoms to diagnosis, we aimed to identify HAE in untested first-degree blood relatives among some of our patients with HAE in our outpatient clinic at Hospital Universitário Clementino Fraga (HUCFF), Federal University of Rio de Janeiro. Methods: Untested first-degree relatives of patients with HAE C1INH, even those who were asymptomatic, were identified and invited to participate. Those who agreed to participate answered a specific questionnaire and had a blood sample collected for complement testing. Results: Fifty untested first-degree relatives of 30 index patients with HAE C1INH were identified, and both groups were analyzed. The mean ± standard deviation (SD) age of the index patients group was 37.08 ± 16.56 years (range, 13-73 years), with a high frequency in women (n = 24 [80.0%]). Most of them had severe (n = 23 [76.7%]) and moderate (n = 7 [23.3%]) attacks. None were asymptomatic. The mean ± SD time between the first symptoms and diagnosis was 20.2 ± 11.06 years (range, 0-48 years) in that group. In the first-degree relatives group, 30 new cases of HAE C1INH (60%) were identified. Conclusion: We found that there was a long time between early manifestations and a diagnosis of HAE. First-degree relatives of patients with HAE patients are at risk for having the disease. Sixty percent were newly diagnosed with HAE and with C1INH deficiency in our study. So, screening of family members, including individuals who were asymptomatic, is the key for earlier diagnosis and effective treatment.

Impact of chronic urticaria on the quality of life of patients followed up at a university hospital

Abstract BACKGROUND: Chronic urticaria is a debilitating disease that considerably affects health-related quality of life, and the Chronic Urticaria Quality of Life Questionnaire is the only questionnaire specifically designed for its evaluation. OBJECTIVE: To evaluate the quality of life of patients with chronic urticaria, using the Brazilian Portuguese version of the Chronic Urticaria Quality of Life Questionnaire. METHODS: The Chronic Urticaria Quality of Life Questionnaire was self-administered in 112 chronic urticaria patients and disease activity was assessed through the Urticaria Activity Score. Clinical and socio-demographic characteristics of patients were studied, such as: age, sex, etiologic diagnosis of chronic urticaria, duration of disease and Urticaria Activity Score. RESULTS: The population studied was composed 85.72% of women with a mean age of 46 years (18-90), while the median disease duration period was 10 years (3 months-60 years). Regarding the etiologic diagnosis, 48.22% had chronic spontaneous urticaria; 22.32% associated with inducible urticaria, 28.57% with chronic autoimmune urticaria, and 23.21% had physical urticaria alone. Disease activity evaluated using the Urticaria Activity Score was 1.04 ± 1.61 (0-6). The total score for the Chronic Urticaria Quality of Life Questionnaire was 36 (0-100) and dimension I (sleep/mental status/eating) had a greater impact on quality of life. The items with the highest mean scores were nervousness and shame over lesions, while the items with the lowest scores were lip swelling and limitations on sporting activities. CONCLUSIONS: Chronic urticaria compromises patients' quality of life, mainly those with more severe disease or who are diagnosed with chronic autoimmune urticaria.

Impact of chronic urticaria on the quality of life of patients followed up at a university hospital.

BACKGROUND:: Chronic urticaria is a debilitating disease that considerably affects health-related quality of life, and the Chronic Urticaria Quality of Life Questionnaire is the only questionnaire specifically designed for its evaluation. OBJECTIVE:: To evaluate the quality of life of patients with chronic urticaria, using the Brazilian Portuguese version of the Chronic Urticaria Quality of Life Questionnaire. METHODS:: The Chronic Urticaria Quality of Life Questionnaire was self-administered in 112 chronic urticaria patients and disease activity was assessed through the Urticaria Activity Score. Clinical and socio-demographic characteristics of patients were studied, such as: age, sex, etiologic diagnosis of chronic urticaria, duration of disease and Urticaria Activity Score. RESULTS:: The population studied was composed 85.72% of women with a mean age of 46 years (18-90), while the median disease duration period was 10 years (3 months-60 years). Regarding the etiologic diagnosis, 48.22% had chronic spontaneous urticaria; 22.32% associated with inducible urticaria, 28.57% with chronic autoimmune urticaria, and 23.21% had physical urticaria alone. Disease activity evaluated using the Urticaria Activity Score was 1.04 ± 1.61 (0-6). The total score for the Chronic Urticaria Quality of Life Questionnaire was 36 (0-100) and dimension I (sleep/mental status/eating) had a greater impact on quality of life. The items with the highest mean scores were nervousness and shame over lesions, while the items with the lowest scores were lip swelling and limitations on sporting activities. CONCLUSIONS:: Chronic urticaria compromises patients' quality of life, mainly those with more severe disease or who are diagnosed with chronic autoimmune urticaria.

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.

Teste de contato atópico com aeroalérgenos: uma ferramenta promissora no diagnóstico da dermatite atópica / Atopy patch test with aeroallergens: a promising tool in the diagnosis of atopic dermatitis

Objetivos: Avaliar a padronização do método com relação à concentração do aeroalérgeno, tempo de oclusão, de interpretação; e determinar a especificidade e a sensibilidade do teste de contato alérgico (TCA) em relação ao teste por puntura e a dosagem de IgE específica, na verificação da sensibilização a ácaros em crianças com dermatite atópica (DA). Métodos: Foram selecionadas 72 crianças com idade entre 2 e 12 anos, acompanhadas no ambulatório de alergia do Hospital São Zacharias. Estas foram submetidas a teste de puntura, dosagem de IgEs específicas e TCA para ácaros (Dermatophagoides pteronyssinus, Dermatophagoides farinae e Blomia tropicalis). Os testes foram realizados em 3 grupos: (1) DA com ou sem rinite e asma, (2) Rinite e/ou asma sem DA, (3) Saudáveis (controle). Resultados: No grupo 1, 40% dos pacientes apresentaram reação positiva. A sensibilidade foi maior nos pacientes com maior tempo de exposição (48 h e 72 h). No grupo 2, o TCA foi mais específico que sensível para todos os extratos, com aumento da sensibilidade quanto maior o tempo de exposição (72 h). No grupo 3, apenas 8,3% apresentaram positividade a algum aeroalérgeno do TCA. Conclusão: O TCA mostrou ter valor diagnóstico em relação às reações de fase tardia a ácaros (D. pteronyssinus, D. farinae e B. tropicalis), com elevada especificidade. Ele demonstrou ser um teste confiável quando comparado aos resultados do grupo controle.

Objectives: To evaluate the standardization of the atopy patch test (APT) with regard toconcentration of aeroallergens, occlusion time, and interpretation, and to determine the specificityand sensitivity of the method in relation to prick test and serum specific IgE determination in theinvestigation of dust mite sensitization in children with atopic dermatitis (AD). Methods: Seventytwo children, ranging from 2 to 12 years of age, were selected among those receiving care at the allergy outpatient clinic of São Zacharias Hospital. Children underwent skin prick testing, specific IgE measurements, and APT for mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae,and Blomia tropicalis). Tests were performed in three groups: (1) AD with or without rhinitis andasthma; (2) rhinitis and/or asthma without AD; (3) healthy individuals (controls). Results: In group 1, 40% of the patients presented positive reactions. Sensitivity was higher in patients with longer exposure times (48 h and 72 h). In group 2, APT was more specific than sensitive for allextracts, with increasing sensitivity associated with longer times of exposure (72 h). In group 3,only 8.3% of the individuals were positive to any aeroallergen on APT. Conclusion: APT seemsto have diagnostic value in identifying late phase reactions to mites (D. pteronyssinus, D. farinae, and B. tropicalis), with high specificity, and proved to be a reliable test when compared with the results obtained for controls.

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 (cow's 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 group's results.

Atopy patch test (APT) in the diagnosis of food allergy in children with atopic dermatitis / Teste de contato atópico (TCA) no diagnóstico de alergia alimentar em crianças com dermatite atópica

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 (cow's 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 group's results.

FUNDAMENTOS: A Dermatite Atópica é uma doença inflamatória crônica da pele. Os alimentos são importantes na patogênese da doença em 1/3 dos casos. Diversos mecanismos estão envolvidos na fisiopatogenia da dermatite Atópica. As reações imediatas são identificadas pela dosagem de IgE específica e teste de puntura. O teste de contato atópico parece ter relevância na investigação de pacientes com suspeita de reação tardia. OBJETIVOS: Avaliar a padronização do método com relação à concentração do alérgeno, tempo de oclusão e de interpretação; e determinar a especificidade e a sensibilidade do teste de contato atópico em relação ao teste de puntura e a dosagem de IgE específica, no diagnóstico de alergia alimentar em crianças com dermatite Atópica. MÉTODOS: Setenta e duas crianças com 2 a 12 anos foram submetidas a teste de puntura e dosagem de IgE específicas para alimentos (leite de vaca, ovo, soja, trigo). O teste de contato atópico foi aplicado em 3 grupos: (1) Dermatite Atópica com ou sem Rinite e Asma; (2) Rinite e ou Asma sem Dermatite Atópica; (3) Saudáveis. RESULTADOS: No grupo 1, 40% dos pacientes apresentaram reação positiva. Quanto maior o tempo de exposição, maior foi a sensibilidade. No grupo 2, o teste foi mais específico que sensível para todos os extratos; com aumento da sensibilidade com maior tempo de exposição (72h). No grupo 3, 8.3% apresentaram testes positivos. CONCLUSÃO: O teste de contato atópico mostrou ter valor diagnóstico em relação às reações de fase tardia a alimentos, com elevada especificidade. Mostrou-se um teste específico e confiável ao comparar com os resultados do grupo controle.

Prevalence of autoantibodies in a group of hereditary angioedema patients.

Hereditary Angioedema is a dominantly inherited disease. Routine screening of autoantibodies (AAB) is not recommended for individuals with Hereditary Angioedema; however, prevalence of these antibodies in Hereditary Angioedema patients is not well documented. We aim to determine the prevalence of AAB so that individuals at risk of developing autoimmune diseases can be identified. Fifteen patients with Hereditary Angioedema attended at Clementino Fraga Filho University Hospital accepted to participate in this study. Prevalence of AAB was 40%. Our data indicate high prevalence of AAB in patients with Hereditary Angioedema. Large-scale studies should be considered to determine the significance of these AAB in the follow-up care of patients with Hereditary Angioedema.

Asma e síndrome de Churg-Strauss / Asthma and Churg-Strauss syndrome

Relata-se o caso de uma mulher de 25 anos com síndrome de Churg-Strauss, cujos sintomas surgiram aos dezesseis anos, logo após o início do uso de contraceptivo oral. O quadro clínico evoluiu rapidamente com asma persistente grave, polipose nasal, rinite perene obstrutiva, eosinofilia periférica e tecidual, e mononeurite. A síndrome de Churg-Strauss é uma doença que exige suspeita precoce, diagnóstico preciso, tratamento agressivo e monitoramento periódico, devendo ser considerada no diagnóstico diferencial de asma persistente moderada e grave. O caso relatado chama a atenção para possível participação hormonal e surgimento em idade precoce.

We report the case of a 25-year-old woman with Churg-Strauss syndrome, the symptoms of which had first appeared soon after she began taking oral contraceptive at the age of sixteen. The clinical profile evolved rapidly to severe persistent asthma, nasal polyposis, perennial obstructive rhinitis, eosinophilia (peripheral/tissue) and mononeuritis. Churg-Strauss syndrome is the type of disease that demands early detection, accurate diagnosis, aggressive treatment and periodic monitoring. It should be considered in the differential diagnosis of moderate and severe persistent asthma. The case reported calls attention to possibility that there is a hormonal component and that the disease can present early onset.

Asthma and Churg-Strauss syndrome.

We report the case of a 25-year-old woman with Churg-Strauss syndrome, the symptoms of which had first appeared soon after she began taking oral contraceptive at the age of sixteen. The clinical profile evolved rapidly to severe persistent asthma, nasal polyposis, perennial obstructive rhinitis, eosinophilia (peripheral/tissue) and mononeuritis. Churg-Strauss syndrome is the type of disease that demands early detection, accurate diagnosis, aggressive treatment and periodic monitoring. It should be considered in the differential diagnosis of moderate and severe persistent asthma. The case reported calls attention to possibility that there is a hormonal component and that the disease can present early onset.