What lessons can we learn? Clinical and epidemiological retrospective analysis of 267 patients with urticaria in a Brazilian tertiary center

Abstract Background: There are few epidemiological studies of urticaria, published in the indexed literature (PubMed/Medline). Objective: The study aimed to evaluate the epidemiological and clinical data among patients with urticaria/angioedema attending a reference clinic in Brazil. Methods: Two hundred sixty-seven patients were evaluated retrospectively considering demographic data, time course of the disease, triggering symptoms, the presence of angioedema, complementary laboratory tests including total blood count, reactive-C protein, erythrocyte sedimentation rate, IgE serum levels, and other, as necessary. Results: The most commonly diagnosed type of urticaria was chronic spontaneous urticaria (56.93%). Angioedema was associated with chronic urticaria in 108 patients (40.08%). Study limitations: Unicentered and retrospective. Conclusion: Some relevant findings in this study are the observation of a female prevalence of cases (4-females: 1-man), a result more elevated than demonstrated in previous studies in Europe and Asia, the median age was 43-years old and the delay of time between the diagnosis of urticaria and the admission for treatment in a specialized center was approximately 2-years. Other multicenter studies can better establish these differences in Brazilian patients.

Episodic angioedema with eosinophilia (Gleich's syndrome) associated with urticarial vasculitis: a coincidence or a novel clinical entity?

Episodic angioedema with eosinophilia (EAE) is a rare condition characterized by recurrent attacks of angioedema and urticaria accompanied by a marked elevation of peripheral eosinophil count. We report the case of a young female patient diagnosed with EAE associated with urticarial vasculitis. A 40-year-old female patient was admitted to our institution due to recurrent episodes of cheek and eyelid angioedema in the previous year. Episodes of facial angioedema lasted for two months with spontaneous remission afterwards. In addition, she presented pruritic and painful skin eruptions of erythematous circles, which persisted for longer than 24 h, that were palpable, somewhat purplish, and more pronounced on the face, arms, and trunk. Laboratory investigation showed a sustained elevation of white cell counts with marked eosinophilia. Serum IgM, IgE, and IgA were normal; IgG was slightly elevated. C1-esterase inhibitor and tryptase test were normal. Reverse transcriptase-polymerase chain reaction was performed for detection of FIP1L1-PDGFRA and BCR-ABL rearrangements. None of these alterations were found. Skin biopsies were suggestive of urticarial vasculitis. The patient was submitted to esophagogastroduodenoscopy, which showed mild chronic gastritis, with no eosinophilic infiltration. Cardiac dimensions and function were normal. Abdominal ultrasound and total body CT-scan failed to show lymphadenopathy, organomegaly, and tumors. We report the first case of association between episodic angioedema with eosinophilia and urticarial vasculitis. It is possible that both conditions share a physiopathological mechanism, suggesting that it is not just a chance association.

Hereditary angioedema: how to approach it at the emergency department? / Angioedema hereditário: como abordar na emergência?

ABSTRACT 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.

RESUMO As crises de angioedema são causas comuns de atendimentos nas emergências, e devido ao potencial de gravidade, é importante que os profissionais que atuam nesses serviços conheçam suas causas e abordagem. Os mecanismos envolvidos no angioedema sem urticas podem ser histaminérgicos ou mediados por bradicinina. As causas mais comuns de angioedema mediado por histamina são alimentos, medicamentos, ferroada de insetos e idiopática. Quando o mediador é a bradicinina, os desencadeantes são os inibidores da enzima conversora de angiotensina e fatores relacionados ao angioedema adquirido com deficiência do inibidor de C1 ou angioedema hereditário que são menos comuns, mas muito importantes pela possibilidade de desfecho fatal. O angioedema hereditário é uma doença rara, caracterizada por crises de edema que acometem o tecido subcutâneo e mucosas de vários órgãos, manifestando-se principalmente por crises de angioedema e dor abdominal. Esse tipo de angioedema não responde ao tratamento usual com adrenalina, anti-histamínicos e corticosteroides. Assim, se não identificados e tratados adequadamente, esses pacientes têm risco de morte por edema de laringe estimado em 25% a 40%. O tratamento do angioedema hereditário mudou drasticamente nos últimos anos, com o desenvolvimento de novos e eficientes fármacos para as crises: inibidor de C1 derivado de plasma, inibidor de C1 recombinante humano, antagonista do receptor B2 da bradicinina (icatibanto) e o inibidor da calicreína (ecalantide). No Brasil, até o momento, estão liberados para uso o inibidor de C1 derivado de plasma e o icatibanto. O manejo correto desses pacientes na emergência evita cirurgias desnecessárias e, principalmente, desfechos fatais.

Angioedème bradykinique d'évolution fatale suite à une prise d'énalapril. A propos d'un cas

L'angiœdème bradykinique est une maladie rare et grave qui constitue une complication exceptionnelle du traitement aux Inhibiteurs de l'Enzyme de Conversion (IEC). Elle engage le pronostic vital des patients dans 75% des cas et représente une urgence médicale majeure. L'évolution de cette affection est totalement imprévisible avec un risque de décès par asphyxie. Les auteurs rapportent l'observation d'une patiente de 70 ans hypertendue qui a présenté un angiœdème bradykinique d'évolution fatale deux jours après l'initiation de son traitement antihypertenseur par les IEC. Au travers cette observation, les auteurs voudraient mettre en lumière cette affection mortelle, de diagnostic difficile souvent méconnue

Anaphylactic reaction/angioedema associated with jellyfish sting

Abstract The most frequent jellyfish in Southern Brazil causes mainly local pain and skin plaques. A 3-year-old female bather presented an erythematous, irregular plaque on the left forearm after contact with a jellyfish and intense facial angioedema with facial flushing. The lungs had vesicular murmur, wheezes, and snorts, and pink and spumous secretion in the airways with intercostal retraction. She was administered subcutaneous adrenaline (0.1mg/kg) and hydrocortisone intravenous (10mg/kg) with total recovery in a few minutes. The manifestations of anaphylactic reactions are distinct from those of envenomations, and prompt and adequate care is fundamental in these situations.

Epidemiology of angioedema without wheals in an allergy and immunology center

We describe the diagnostic epidemiology, the clinical course, the family history and the response to treatment of patients with angioedema without wheals (AWW) at an Allergy and Immunology Clinical Center. We reviewed the case records of all patients at our office from January 1997 to April 2013. We recorded sex, age, age at onset of symptoms, family history of angioedema, number of visits to the office, type of angioedema, and response to treatment from those patients with angioedema without wheals. We classified angioedema according to its pathophysiology. We also describe those patients with angioedema mimics. From a total of 17 823 new patients, 303 had a presumptive diagnosis of angioedema without wheals. Twenty-three patients had an angioedema mimic. Forty percent were male and 60% were female. Average age at first visit was 40.6. Average number of visits was 2.4. Fifty-seven patients referred a family history. We attributed idiopathic angioedema to 55.7% of patients, 24.3% were drug related, 15.7% were due to C1 inhibitor deficiency, 2.1% were drug related + idiopathic angioedema, 1.4% were type III and 0.7% had exercise-induced angioedema. Ninety six percent of 53 evaluable idiopathic angioedema patients referred a benefit with anti-histamine therapy. AWW was a rare cause of consultation. Most of our patients had anti H1 responsive idiopathic angioedema and none had allergic angioedema. Women cases prevailed over men´s. Family history and average age of onset of symptoms were different among the different types of angioedema.

Describimos la epidemiología, historia clínica, antecedentes familiares y respuesta al tratamiento de los pacientes consultando por angioedema sin urticaria en nuestra clínica especializada en Alergia e Inmunología. Revisamos retrospectivamente todas las historias clínicas de nuestro consultorio entre enero de 1997 y abril de 2013. Seleccionamos aquellos pacientes que habían consultado por angioedema sin urticaria y registramos el sexo, edad, edad de comienzo de síntomas, antecedentes familiares de angioedema, número de consultas, tipo de angioedema y respuesta al tratamiento. Clasificamos el angioedema de acuerdo a su fisiopatología. Describimos también los diagnósticos diferenciales que encontramos. De un total de 17 823 pacientes, 303 consultaron por angioedema sin ronchas. Veintitrés presentaban un diagnóstico alternativo. El 40% eran hombres y el 60% mujeres. La edad promedio de la primera visita fue 40.6 años. El promedio de consultas fue 2.4. Cincuenta y siete refirieron antecedentes familiares. El 55.7% fue clasificado como angioedema idiopático, el 24.3% secundario a drogas, el 15.7% secundario a deficiencia del inhibidor C1, 2.1% por drogas + idiopático, 1.4% angioedema tipo III y 0.71% asociado al ejercicio. Noventa y seis por ciento de 53 pacientes evaluables con angioedema idiopático se beneficiaron con antihistamínicos. El angioedema sin urticaria fue una causa rara de consultas. Las mujeres prevalecieron sobre los hombres. Los antecedentes familiares y la edad de comienzo de síntomas variaron de acuerdo al tipo de angioedema.

Angioedema por enalapril: caso clínico / Enalapril angioedema: clinical case

La prescripción de inhibidores de la enzima convertidora de angiotensina (IECA), en el manejo de la hipertensión e insuficiencia cardíaca se ha incrementado fuertemente desde su introducción en 1980. Estas drogas son consideradas seguras, pero se sabe que pueden producir angioedema severo como efecto secundarop en el 0.1 a 0.3% de los pacientes tratados. Caso clínico: paciente de sexo masculino de 57 años de edad, con diagnóstico de hipertensión arterial, tratado con Enalapril 20mg/día, desde hacía 7 días. Ingresa por guardia presentando angioedema en zona bipalpebral, bilateral; labio superior e inferior y regiones malares. No representa compromiso respiratorio. Dentro de sus antecedentes niega alergia a medicamentos y/o alimentos. Se indica como tratamiento Hidrocortisona y Difenhindramina (EV), evolucionando favorablemente, por lo que es externado indicándose Prednisona y Fexofenadina (OV). Dentro de las 48 hs. siguientes concurre a control, encontrandosé asintomático. Discusión: El mecanismo por el cual los inhibidores de la angiotensina producen angioedema no es claro pero probablemente sería por una acumulación tisular de bradiquinina. El angioedema generalmente afecta cabeza y cuello, por lo tanto la vía aérea está en riesgo. Ante un paciente con angioedema tratado con IECA, debería considerarse como primera causa a la administración del medicamento ya que la misma puede presentarse a los días, meses e incluso años de comenzado el tratamiento. Conclusión: El desafío para futuras investigaciones es identificar los subgrupos de pacientes con mayor riesgo de presentar angioedema, en quienes el riesgo de recibir terapia con IECA es mayor que el beneficio.

Prescription of angiotensin convertidara inhibitors (ACE) in the management of hypertension and heart failure has increased rapidly since its introduction in 1980. These drugs are considered to be safe, but it is known that can produce severe angioedema as side effect in 0.1 to 0.3% of treated patients. Clinical Case: A 57 years old male patient was admitted to the emergency department because angioedema in the bipalpebral and bilateral areas as well as in the upper and cheek regions. He had a diagnosis of hypertension and had been taking enalapril 20mg/day, for the previous 7 days. There was no respiratory compromise. He denied history of drug and / or food allergies. Hydrocortisone and Difenhindramina (EV) were prescribed with a favourable outcome. The patient was discharged with indications of prednisone and fexofenadine (OV). At a follow-up visit, 48 hours later, he presented no symptoms. Discussion: The mechanism by which inhibitors of angiotensin produced angioedema is unclear but would probably be by a tissue accumulation of bradykinin. Angioedema usually affects the head and neck so the airway is at risk. In patients with angioedema and ACE inhibitors treatment, IECA should be considered as first cause. It can occur days, months and even years of after the beginning of treatment. Conclusion: The challenge for future research is to identify subgroups of patients at increased risk of angioedema, in whom the risk of receiving ACE inhibitor therapy is greater than the benefit.

Angioedema: a diagnostic dilemma / Angioedema: um diagnóstico dilema

Introduction: Angioedema is a rare but potentially life threatening (fatal laryngeal edema) disease. It is a relapsing subcutaneous or submucosal edema caused by various factors. The episodes can vary significantly from one individual to another. Causative factors should always be sought, but a large proportion of patients have the idiopathic form of the disease. A minority of patients represent a diagnostic and treatment challenge. A comprehensive history and close monitoring of response to treatment are the most cost effective diagnostic and treatment tools. Objective: This paper presents a highly representative clinical case of idiopathic variety of the disease where a ten year old boy reported with a complaint of swelling over right side of the face and upper lip since 4 hours. Conclusion: There was no associated pain or discomfort. There was slight itching in the same area prior to the appearance of swelling. Condition showed prompt improvement following antihistamines.

Introdução: Angioedema é uma doença rara, porém, com potencial risco à vida (edema fatal de laringe).É um edema subcutâneo ou submucoso recidivante causado por vários fatores. Os episódios podem variar significativamentede um indivíduo para outro. Fatores causadores da doença sempre devem ser pesquisados, mas uma grande proporção dos pacientes tem a forma idiopática da doença. Uma minoria de pacientes representaum desafio no diagnóstico e tratamento. O histórico completo e o acompanhamento da resposta ao tratamentosão as ferramentas de diagnóstico e tratamento de menor custo. Objetivo: Este trabalho apresenta um casoclínico altamente representativo da variedade idiopática da doença: um menino de dez anos se apresentou comqueixa de inchaço no lado direito da face e no lábio superior nas últimas 4 horas. Conclusão: Não havia dorassociada ou desconforto, havia leve coceira na mesma área, anterior ao aparecimento de inchaço. A condiçãomostrou rápida melhora após medicação com anti-histamínicos.

Angioedema cervical / Cervical angioedema: report of one case

Se presenta el caso de una mujer en la edad media de la vida, hipertensa en tratamiento, con el antecedente de cirugía bariátrica, que desarrolla cuadro de masa cervical asintomática en la que, luego de descartar otras patologías por imágenes y evolución, se diagnosticó Angioedema cervical, el que tuvo regresión total, prácticamente espontánea, en los días siguientes.

We report a 45 years old woman with a history of high blood pressure and bariatric surgery that consulted for painless sweiling of the cervical region and upper chest. A CAT sean informed an extensive edema involving the lower neck and the superior anterior mediastinum and lytic lesions in the cervical spine. An angioedema was diagnosed, and edema disappeared in five days. After one month of follow up, the patient is in good conditions.

Sociodemographic and clinical characteristics, causal factors and evolution of a group of patients with chronic urticaria-angioedema

CONTEXT AND OBJECTIVE: Chronic urticaria-angioedema is a common, multiple-cause complaint. The aim was to investigate the sociodemographic and clinical characteristics, causal and aggravating factors and evolution of urticaria-angioedema. DESIGN AND SETTING: This was a descriptive prospective study carried out at the Dermatology outpatient clinic of Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp). METHODS: A total of 125 patients with chronic urticaria-angioedema were evaluated to obtain sociodemographic data, anamnesis, dermatological and general clinical data and laboratory data, emphasizing causal and aggravating factors and complaint evolution. RESULTS: Chronic urticaria-angioedema occurred mainly in females (mean age: 35 years), but also in men (mean age: 32 years). White color and living in urban areas also predominated. There was no preferential time for symptoms to appear, and nighttime was the most commonly reported time for clinical worsening. Around half of the patients had urticaria associated with angioedema. There were no associated factors in most of the cases, and stress was the most commonly reported aggravating factor. The cause was ascertained in 37.6 percent of our cases. The mean duration of follow-up was 11.7 months. Around 60 percent of the patients evolved with the problem under control, 32 percent improved, 9 percent had no change in dermatological condition and only one patient worsened. CONCLUSIONS: Chronic urticaria-angioedema was more common among middle-aged women. It is a long-term disease, and its cause was explained in about one-third of the patients. Half of the patients presented disease control after treatment lasting an average of approximately one year.

CONTEXTO E OBJETIVO: Urticária-angioedema crônico é enfermidade freqüente, complexa e multicausal. O objetivo foi estudar as características sociodemográficas, clínicas, os fatores causais, agravantes e a evolução da enfermidade. TIPO DE ESTUDO E LOCAL: Descritivo e prospectivo, realizado no ambulatório de Dermatologia da Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp). MÉTODOS: Foram avaliados pacientes com diagnóstico de urticária-angioedema crônico através de dados sociodemográficos, anamnese, exames dermatológico, clínico e laboratorial, com ênfase nos fatores causais, agravantes e na evolução da enfermidade. RESULTADOS: 125 pacientes foram incluídos, 95 mulheres e 30 homens. Predominaram mulheres de 30 a 40 anos e homens de 10 a 20 anos. A idade média foi de 35 anos para as mulheres e 32 anos para os homens. Predominaram pacientes de raça branca, residentes em zona urbana e casados. O tempo médio de doença foi de 45,6 meses e de cada lesão foi de 5,6 horas. A metade dos casos tinha surtos diariamente e associação de urticária com angioedema. Não houve horário preferencial de aparecimento dos surtos, mas o noturno foi o horário de piora mais citado. A causa foi esclarecida em 37,6 por cento, predominando as infecções. O estresse foi o agravante mais referido. O tempo médio de acompanhamento foi de 11,7 meses e 60 por cento evoluíram para o controle, 32 por cento melhoraram, 9 por cento mantiveram-se inalterados e um caso piorou. CONCLUSÕES: Urticária-angioedema ocorreu mais em mulheres de meia-idade. A causa foi esclarecida em um terço dos pacientes e metade deles teve controle da doença em aproximadamente um ano.

Urticaria and angioedema in Siriraj medical students.

The present study aimed to investigate the current prevalence of urticaria with or without angioedema among Siriraj medical students, the possible causative agent(s), the association between a history of atopy, behavior of patients seeking treatment and natural course. A cross-sectional study was conducted among 428 Siriraj medical students, Mahidol University in October, 2001. The study showed the prevalence of urticaria and angioedema to be 51.6 per cent and 19.6 per cent respectively, coexisting in 13.6 per cent but urticaria alone occurred in 38 per cent and angioedema alone in 6 per cent. There was an equal sex distribution. Acute urticaria (93.2%) was more prevalent than chronic urticaria (5.4%), and the acute intermittent type was the most common. Heat, inhalants, and contactants were more often suspected causes than food or drug allergy identified in both forms. More than half the urticaria subjects treated themselves by buying over-the-counter drugs (66%) and the remainder waited for spontaneous remission (49%) with a low percentage seeking medical advice (24% from a general practitioner, 14% from a dermatologist). An atopic history was not a major underlying factor for urticaria. Most patients with acute urticaria were free of symptoms after 3 weeks. Cases with chronic urticaria who were completely healed had a mean disease duration of 14.2 weeks. However, cases with chronic urticaria who had never had a long hive free period since the onset of the disease until the time of the study had a mean disease duration of 6 years. These findings may be useful to help educate affected persons and improve public awareness in order to prevent and manage this disease.

Urticária e doenças sistêmicas / Systemic diseases and urticari

Chronic urticaria and concurrent angioedema are disappoiting problems for both physicians and patients. The disease can result from multiple causes and probably does not have a single etiology. Several factors have been identified that appear to be important in the pathogenesis of individual cases, some drugs, food additives, physical factors and internal diseases. In some cases no pathogenesis are identified and those cases are classified as idiopathic. In recent years several articles has emphasized autoimmunity and infections due to Helicobacter pylori. Our article reviewed the etiology of chronic urticari at current concepts.

Síndrome de la vena cava superior: diagnóstico diferencial del edema angioneurótico / Superior vena caval syndrome: differencial diagnosis of angioneurotic edema

Presentamos el caso de un paciente, fumador de dos paquetes/día, que acudió a un servicio médico de urgencias refiriendo un cuadro de tres días de evolución de disnea y edema facial y palpebral. Con el diagnóstico de edema angioneurótico es remitido a nuestro servicio para estudio. A la exploración física el paciente presentaba un edema cérvico-facial y palpebral, así como una ingurgitación de las venas yugulares. En la parte superior del tórax se evidenciaron dilataciones varicosas de las venas superficiales. Con el diagnóstico de sospecha de síndrome de la vena cava superior (SVCS), se realizó una radiografía de tórax, en la que se objetivaron una masa pulmonar y un ensanchamiento mediastínico. Tras realizar una biopsia transbronquial mediante fibrobroncoscopía, se establece el diagnóstico de carcinoma broncogénico de células pequeñas (oat-cell). Se comentan la etiología, diagnóstico diferencial y tratamiento del SVCS