Guia prático de urticária para grupos especiais de pacientes / Practical guide to urticaria for special patient groups

A urticária crônica é uma condição que afeta mais de um milhão de brasileiros, com grande impacto na qualidade de vida. Mesmo com diretrizes bem difundidas para o seu diagnóstico e tratamento, seu manejo pode ser desafiador em pacientes pediátricos, idosos e gestantes. Para auxiliar o médico especialista nestes casos, o Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia elaborou esta revisão com as principais dúvidas e dificuldades referentes ao tema nestes grupos de pacientes.

Chronic urticaria is a condition that affects more than a million Brazilians with a significant impact on quality of life. Although there are well-established guidelines for diagnosis and treatment, the management of chronic urticaria may be challenging in pediatric, older, and pregnant patients. With the purpose of helping specialists manage these cases, the Urticaria Scientific Department of the Brazilian Association of Allergy and Immunology prepared this review with the most common doubts and difficulties about this topic in those patient groups.

Guia prático de urticária aguda / Practical guide to acute urticaria

A urticária aguda é uma causa frequente de consulta com alergistas, caracterizada por urticas e/ou angioedema. Embora autolimitada e benigna, pode causar desconforto significativo e raramente representar uma doença sistêmica grave ou reação alérgica com risco de vida. Nesta revisão, elaborada pelo Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia, foram abordadas as principais questões referentes ao tema para auxiliar o médico especialista e generalista.

Acute urticaria is a frequent cause of consultations with allergists, being characterized by wheals and/or angioedema. Although self-limited and benign, it may cause significant discomfort and uncommonly represent a serious systemic disease or life-threatening allergic reaction. In this review prepared by the Urticaria Scientific Department of the Brazilian Association of Allergy and Immunology, the main questions about this topic are addressed to help specialists and general practitioners.

Application of capillary zone electrophoresis to determine second-generation H1 antihistaminic drugs, loratadine and rupatadine

Abstract The second generation of H1 antihistamines from the piperidine group are often used for treating allergic diseases due to their action on histaminic receptors, the primary mediator of allergy. Moreover, the antihistamines have anti-inflammatory action, mediated through platelet-activating factor blocking activity. A simple and rapid capillary zone electrophoresis method was developed and validated for the determination of loratadine (LOR) and rupatadine (RUP) in tablets. The analyses were carried out using a fused silica capillary of 50.2 cm (40 cm effective length), 75 µm i.d. The background electrolyte was composed of boric acid 35 mmol/L, pH 2.5. Voltage of 20 kV, hydrodynamic injection of 3447.3 Pa for 3s, temperature at 25 ºC, and UV detection at 205 nm were applied. Electrophoretic separation was achieved at 1.8 and 2.8 min for RUP and LOR, respectively. The method was linear for both drugs in a range of 50.0 to 400.0 µg/mL (r>0.99). The limits of detection and quantification were 46.37 and 140.52 µg/mL, for LOR and 29.60 and 89.69 µg/mL for RUP respectively. The precision was less than 5.0 % for both drugs. The average recovery was approximately 100 %. The proposed novel method can significantly contribute to the rapid detection of counterfeit products and in quality control of drug products containing antihistamines

Dupilumabe na urticária crônica espontânea refratária ao omalizumabe / Dupilumab in chronic spontaneous urticaria refractory to omalizumab

A urticária é uma lesão cutânea eritematosa, edematosa e pruriginosa, mais prevalente em mulheres entre 30 a 50 anos de idade, sendo classificada em aguda ou crônica. O quadro clínico da urticária crônica espontânea é desencadeado independentemente de estímulos exógenos, podendo ser acompanhado de angioedema em 40% dos casos. O diagnóstico é clínico e a doença pode ser monitorada com escores. O tratamento da urticária crônica espontânea é baseado em anti-histamínicos H1 de segunda geração como primeira linha. A segunda linha se baseia no aumento da dose de anti-histamínicos H1 em até quatro vezes a dose habitual, a terceira linha consiste na associação de imunobiológicos como o omalizumabe, e a quarta linha no uso de ciclosporina. Este relato de caso teve como objetivo analisar a eficácia e segurança do tratamento com dupilumabe na urticária crônica espontânea refratária ao omalizumabe, utilizando os escores de atividade da urticária e o questionário de qualidade de vida em dermatologia. A partir dos resultados obtidos, verificou-se sucesso terapêutico com dupilumabe, que se manteve mesmo após suspensão do medicamento. O uso off label do dupilumabe justificou-se pelo seu mecanismo de ação na fisiopatologia da doença. Este é o primeiro relato de caso brasileiro do uso de dupilumabe para urticária crônica espontânea refratária ao omalizumabe.

Urticaria is an erythematous, edematous, and pruritic skin lesion, most prevalent in women between 30 and 50 years of age, and classified as acute or chronic. The clinical features of spontaneous chronic urticaria are triggered regardless of exogenous stimuli and may be accompanied by angioedema in 40% of cases. The diagnosis is clinical and the disease can be monitored with scores. The first-line treatment of spontaneous chronic urticaria is based on second-generation H1 antihistamines. The second-line treatment is based on increasing the dose of H1 antihistamines by up to four times the standard dose, the third line consists of the association with biologics such as omalizumab, and the fourth line consists of the use of cyclosporine. The present case report aimed to analyze the efficacy and safety of dupilumab treatment for chronic spontaneous urticaria refractory to omalizumab, quantifying clinical improvement and quality of life using urticaria activity scores and a dermatology quality of life questionnaire, respectively. The results obtained showed therapeutic success with dupilumab, which was maintained even after drug suspension. Offlabel use of dupilumab was justified by its mechanism of action in the pathophysiology of the disease. This is the first Brazilian case report of the use of dupilumab for chronic spontaneous urticaria refractory to omalizumab.

Recomendaciones para el diagnóstico y tratamiento de la urticaria en pediatría / Recommendations for the diagnosis and treatment of urticaria in children

La urticaria es una de las afecciones cutáneas más comunes en niños. Se define urticaria aguda cuando persiste hasta 6 semanas, y crónica, cuando la duración es mayor. Afecta al 25 % de la población. La forma aguda es la más frecuente. La crónica representa el 0,1 %, con mayor predominio en mujeres (el 60 %). Se subdivide en urticaria crónica inducible cuando hay un desencadenante externo específico y urticaria crónica espontánea si este no está presente.Aunque la fisiopatología es compleja, la degranulación del mastocito se considera un evento clave. Los antihistamínicos anti-H1 de segunda generación son la primera línea de tratamiento tanto en la urticaria aguda como en la crónica. En pacientes no respondedores, se considerarán otras terapias.Se hará énfasis en urticaria crónica dada la dificultad en su diagnóstico, el aumento de su prevalencia y la gran afectación que produce en la calidad de vida de los niños.

Urticaria is one of the most common skin disorders in children. We define acute urticaria when it persists for less than 6 weeks, and chronic urticaria (CU), when it persists longer. Urticaria affects 25 % of the population; in most cases, it is acute urticaria. CU represents 0.1 %, with higher prevalence in women (60 %). CU is subclassified in chronic inducible urticaria when there is a specific external trigger and chronic spontaneous urticaria if it is not present.Although the pathophysiology is complex, mast cell degranulation is recognized as a key event. Second-generation H1 antihistamines are the first line of treatment in both, acute urticaria and CU. In unresponsive patients, other therapies will be considered.We will emphasize in CU due to the difficulty in its diagnosis, the increase in its prevalence and the severe impairment it causes in children ́s quality of life.

Urticária crônica espontânea de difícil tratamento: existiria um lugar para usar dapsona na falta de omalizumabe? / Spontaneous chronic urticaria of difficult treatment: is there a place to use dapsone in the lack of omalizumab?

Muitos estudos sugerem que a urticária crônica espontânea (UCE) seja uma doença autoimune. A primeira linha de tratamento consiste no uso de anti-histamínicos H1 de segunda geração, que podem ser empregados em até quatro vezes a dose recomendada. A Dapsona ­ diaminodifenil sulfona (DDS) ­ é um quimioterápico com propriedades antimicrobianas e anti-inflamatórias. Em dermatologia, a DDS é usada em doenças nas quais predominam neutrófilos. O omalizumabe é um anticorpo monoclonal, que se liga às moléculas de IgE na circulação e impede que estas IgEs se liguem aos seus receptores. Omalizumabe é recomendado como terceira linha de tratamento de pacientes com UCE, refratários a anti-histamínicos em doses quadriplicadas, na dose de 300 mg a cada quatro semanas. Paciente do sexo feminino, com 41 anos, com UCE sem períodos de remissão por mais de um ano, tratada sem sucesso, com diferentes anti-histamínicos. Existia uma extensa investigação laboratorial. Foi-lhe administrada Cetirizina (anti-histamínico H1 de segunda geração), em elevada dose (40 mg/dia) associada a antileucotrieno (10 mg/dia) por um período de duas semanas. No final do período, a UCE manteve-se completamente inalterada. Foi realizada biopsias das urticas com diagnóstico histopatológico "Dermatite neutrofílica com infiltrado intersticial neutrofílico, sem vasculite ativa e sem eosinófilos". Na falta de omalizumabe, a paciente continuou o tratamento com Cetirizina (40 mg/dia), agora associado a 100 mg/dia de DDS. Atualmente, após 16 semanas de observação, seu quadro mantém-se estável, com urticas ausentes, afora alguns surtos leves, intermitentes. Poder-se-ia usar a DDS na UCE refratária a anti-histamínicos? Alguns estudos bem conduzidos oferecem essa oportunidade.

Many studies suggest that chronic spontaneous urticaria (CSU) is an autoimmune disease. The first line of treatment consists of the use of second-generation H1 antihistamines, which can be used at up to four times the recommended dose. dapsone ­ diaminodiphenyl sulfone (DDS) ­ is a chemotherapeutic agent with antimicrobial and anti-inflammatory properties. In dermatology, DDS is used to treat diseases in which neutrophils predominate. Omalizumab is a monoclonal antibody that binds to IgE molecules in the circulation and prevents these IgEs from binding to their receptors. Omalizumab is recommended as a third-line treatment for patients with CSU refractory to antihistamines in quadruplicate doses, at a dose of 300 mg every four weeks. A 41 year-old female patient with CSU without remission periods for more than one year was unsuccessfully treated with different antihistamines. An extensive laboratory investigation was conducted. She was given a high dose (40 mg/day) of cetirizine (second-generation H1 antihistamine) associated with antileukotriene (10 mg/ day) for a period of two weeks. At the end of the period, CSU remained completely unchanged. Wheal biopsies were performed, with histopathological diagnosis: neutrophilic dermatitis with neutrophilic interstitial infiltrate, without active vasculitis and without eosinophils. In the absence of omalizumab, the patient continued treatment with cetirizine (40 mg/day), now associated with 100 mg/day of DDS. Currently, after 16 weeks of observation, her condition remains stable and the wheals disappeared, apart from some mild, intermittent outbreaks. Could DDS be used in the CSU refractory to antihistamines? Some well-conducted studies offer this opportunity.

Synergistic Effect of H1-Antihistamines on Topical Corticosteroids for Pruritus in Atopic Dermatitis: A Systematic Review and Meta-Analysis

BACKGROUND: Although oral antihistamines (H1-histamine receptor antagonists) are the main treatment option for pruritus in general skin dermatosis, their effect in treating pruritus of atopic dermatitis (AD) has not yet been established. OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the effectiveness of combined therapy of H1-antihistamines and topical steroids. METHODS: We systematically searched MEDLINE, Embase, and CENTRAL databases for articles published from 1967 to 2015. We identified 1,206 studies and assessed their titles, abstract, and full-text. Random effects meta-analysis was used to calculate mean differences (MD) with 95% confidence intervals (CI). RESULTS: Two studies satisfying the inclusion criteria of antihistamine therapy with mandatory topical steroid use were selected. Comparing antihistamine monotherapy with combination therapy, patients treated with the addition of antihistamine to topical corticosteroids showed a statistically significant clinical improvement (standard MD, −0.24; 95% CI, −0.42 to −0.05; p=0.01). CONCLUSION: H1-antihistamines may have a synergistic effect when combined with topical steroids by influencing various associative factors of chronic pruritus in AD.

Conhecimento de farmacêuticos sobre rinite alérgica e seu impacto na asma (guia ARIA para farmacêuticos): um estudo piloto comparativo entre Brasil e Paraguai / Knowledge of allergic rhinitis and its impact on asthma among pharmacists (ARIA guidelines for pharmacists): a comparative pilot study in Brazil and Paraguay

Introdução: Os farmacêuticos, geralmente, são os primeiros profissionais a atenderem pacientes com rinite alérgica (RA). A guia ARIA (Rinite Alérgica e seu Impacto na Asma) estabelece padrões de melhores práticas para o manejo de pacientes com RA. Objetivo: Avaliar o nível de conhecimento sobre RA e a guia ARIA entre farmacêuticos do Brasil (BR) e Paraguai (PY). Método: 205 farmacêuticos (BR = 78, PY = 127) responderam ao questionário online autoaplicável (ARIA One Airways) sobre dados pessoais, profissionais e conhecimento sobre RA e guia ARIA, empregando o Google Forms. Resultados: A mediana de idade foi 32 anos, 35% BR e 52% PY referiam terem tido mais de quatro anos de treinamento. Embora reconheçam os principais sintomas de RA, 26% BR e 100% PY nunca perguntaram se o paciente tinha diagnóstico médico de RA; 20,5% BR e 100,0% PY se os sintomas ocorreram quando perto de animais ou alérgenos; 55% BR e 76% PY se o paciente tinha diagnóstico médico de asma; 59% BR e 70% PY se a rinite piora os sintomas de asma. Anti-histamínicos sedantes foram recomendados por 34,6% BR e 26,8% PY, e corticosteroides intranasais por 59% BR e 52% PY. Embora 85% BR e 100% PY desconheçam as diretrizes ARIA, 94,9% BR e 60,6% PY encaminhariam o paciente a um especialista. Conclusão: Embora os farmacêuticos sejam os primeiros profissionais procurados pelo paciente com RA para alívio de sintomas, o seu nível de conhecimento sobre RA e a guia ARIA é baixo. O seu treinamento para atingir melhor abordagem clínica é primordial.

Introduction: Pharmacists are usually the first professionals to see patients with allergic rhinitis (AR). The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines establish best practice standards for the management of patients with AR. Objective: To evaluate the level of knowledge of AR and ARIA guideline recommendations among pharmacists in Brazil (BR) and Paraguay (PY). Method: A total of 205 pharmacists (BR = 78, PY = 127) answered a self-administered online questionnaire (ARIA One Airways), using the Google Forms tool, containing questions covering personal data, professional data, and knowledge of AR and ARIA guidelines. Results: Median age was 32 years; 35% BR and 52% PY reported having had more than four years of training. Although they recognized the main symptoms of AR, 26% BR and 100% PY never asked whether the patient had a medical diagnosis of AR; 20.5% BR and 100.0% PY if symptoms occurred when close to animals or allergens; 55% BR and 76% PY if the patient had a medical diagnosis of asthma; 59% BR and 70% PY if rhinitis worsened asthma symptoms. Sedating antihistamines were recommended by 34.6% BR and 26.8% PY, and intranasal corticosteroids by 59% BR and 52% PY. Although 85% BR and 100% PY were unaware of ARIA guidelines, 94.9% BR and 60.6% PY would refer the patient to a specialist. Conclusion: Even though pharmacists are the first professionals sought by patients with AR for symptom relief, their level of knowledge of AR and ARIA guidelines is very low. Training is paramount to improve clinical management of AR among pharmacists.

Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil

Abstract: Background: Several dermatoses are mediated by histamine, such as urticaria, angioedema, and papular urticaria. There are no Brazilian studies comparing the potency of antihistamines. Objectives: To evaluate the tolerability and efficacy of the main commercial brand and generic H1 antihistamines, regarding the suppression of the wheal and flare to the histamine test. Methods: A quasi-experimental, open study with 10 healthy adults submitted to the histamine test on the ventral aspect of the forearms. After 20 minutes, wheal and flares were measured. The tests were performed after two hours of intake of dexchlorpheniramine, hydroxyzine, levocetirizine, fexofenadine, cetirizine, loratadine, ebastine, desloratadine, epinastine and rupatadine, as well as generics of loratadine, cetirizine and fexofenadine. Results: All antihistamines presented a reduction in the wheal compared to the control (p <0.02), as well as in the flare, except for rupatadine (p = 0.70). In the internal comparison, cetirizine, fexofenadine, epinastine, levocetirizine, dexchlorpheniramine and hydroxyzine were the most potent, with no difference between them (p > 0.1). As for halo, cetirizine, epinastine, hydroxyzine and fexofenadine were the most potent, with no difference between them (p > 0.1). The most common adverse effect was drowsiness, which was more prevalent among first-generation drugs (p < 0.01). Generic loratadine, fexofenadine and cetirizine halos were higher than their controls (p <0.03).. Study limitations: A single-center study evaluating only aspects related to histamine. Conclusions: Brazilian commercial antihistamines presented different profiles of inhibition of wheal and flares in the histamine test, as well as adverse effects. Generic loratadine, fexofenadine and cetirizine presented larger flares than brand drugs.

Investigation of the antioxidant effects of pheniramine maleate and nebivolol on testicular damage in rats with experimentally induced testis torsion

Abstract Purpose: To investigate the biochemical, histopathologic, and spermatogenetic changes in the detorsionated testicle after experimental torsion and to study the antioxidant effects of pheniramine maleate and nebivolol. Methods: Twenty-four Sprague-Dawley male rats were divided into 4 groups: Group 1: Sham; Group 2: Torsion/Detorsion (T/D); Group 3: T/D + Pheniramine maleate (PM); Group 4: T/D + Nebivolol (NB) group. Paroxanase (PON), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stres index (OSI) were measured, and spermatogenetic and histopathologic evaluation was performed in tissue and blood samples. Results: The evaluation of tissue TAS indicated no statistically significant difference in Group 3 compared to Group 2. A statistically significant increase was detected in Group 4 compared to Group 2. Serum PON levels revealed a statistically significant increase in Groups 3 and 4 compared to Groups 1 and 2. The Johnsen testicular biopsy score decreased in Groups 3 and 4, but the decrease was not statistically significant. Conclusions: Pheniramine maleate and nebivolol have antioxidant effects against ischemia-reperfusion damage. They also support tissue recovery, which is more significantly observed by nebivolol.

Cyproheptadine Regulates Pyramidal Neuron Excitability in Mouse Medial Prefrontal Cortex / 神经科学通报·英文版

Cyproheptadine (CPH), a first-generation antihistamine, enhances the delayed rectifier outward K current (I) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH (10 µmol/L) significantly reduced the current density required to generate action potentials (APs) and increased the instantaneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential (RMP), decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mimicked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium (TEA) to block I channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive I channels as well as other TEA-insensitive K channels, probably I and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.

Mechanisms of histamine ameliorating memory impairment induced by pentylenetetrazole-kindling epilepsy in rats / 浙江大学学报·医学版

To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all<0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all<0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all<0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.

The effect of pheniramine on fentanyl-induced cough: a randomized, double blinded, placebo controlled clinical study / Efeito de feniramina sobre a tosse induzida por fentanil: estudo clínico, randômico, duplo-cego e controlado com placebo

Abstract Background and objectives: There are many studies conducted on reducing the frequency and severity of fentayl-induced cough during anesthesia induction. We propose that pheniramine maleate, an antihistaminic, may suppress this cough. We aim to observe the effect of pheniramine on fentanyl-induced cough during anesthesia induction. Methods: This is a double-blinded, prospective, three-arm parallel, randomized clinical trial of 120 patients with ASA (American Society of Anesthesiologists) physical status III and IV who aged ≥18 and scheduled for elective open heart surgery during general anesthesia. Patients were randomly assigned to three groups of 40 patients, using computer-generated random numbers: placebo group, pheniramine group, and lidocaine group. Results: Cough incidence differed significantly between groups. In the placebo group, 37.5% of patients had cough, whereas the frequency was significantly decreased in pheniramine group (5%) and lidocaine group (15%) (Fischer exact test, p = 0.0007 and p = 0.0188, respectively). There was no significant change in cough incidence between pheniramine group (5%) and lidocaine group (15%) (Fischer exact test, p = 0.4325). Cough severity did also change between groups. Post Hoc tests with Bonferroni showed that mean cough severity in placebo differed significantly than that of pheniramine group and lidocaine group (p < 0.0001 and p = 0.009, respectively). There was no significant change in cough severity between pheniramine group and lidocaine group (p = 0.856). Conclusion: Intravenous pheniramine is as effective as lidocaine in preventing fentayl-induced cough. Our results emphasize that pheniramine is a convenient drug to decrease this cough.

Resumo Justificativa e objetivos: Há muitos estudos sobre a redução da frequência e da gravidade da tosse induzida por fentanil durante a indução da anestesia. Propomos que maleato de feniramina, um anti-histamínico, pode suprimir essa tosse. Nosso objetivo foi observar o efeito de feniramina sobre a tosse induzida por fentanil durante a indução da anestesia. Métodos: Este é um estudo clínico prospectivo, de três braços paralelos, randômico e duplo-cego, de 120 pacientes com estado físico ASA III e IV (de acordo com a Sociedade Americana de Anestesiologistas), ≥ 18 anos e programados para cirurgia cardíaca aberta eletiva sob anestesia geral. Os pacientes foram divididos aleatoriamente em três grupos de 40 pacientes cada, com números aleatórios gerados por computador: grupo placebo, grupo feniramina e grupo lidocaína. Resultados: A incidência de tosse diferiu significativamente entre os grupos. No grupo placebo, 37,5% dos pacientes apresentaram tosse, enquanto que a frequência foi significativamente reduzida no grupo feniramina (5%) e no grupo lidocaína (15%) (teste exato de Fischer, p = 0,0007 e p = 0,0188, respectivamente). Não houve alteração significativa na incidência de tosse entre os grupos feniramina (5%) e lidocaína (15%) (teste exato de Fischer, p = 0,4325). A gravidade da tosse também alterou entre os grupos. Testes post hoc com Bonferroni mostraram que a média da gravidade da tosse no grupo placebo diferiu significativamente das médias dos grupos feniramina e lidocaína (p < 0,0001 e p = 0,009, respectivamente). Não houve alteração significativa na gravidade da tosse entre o grupo feniramina e grupo lidocaína (p = 0,856). Conclusão: Feniramina por via intravenosa tem a mesma eficácia que lidocaína na prevenção da tosse induzida por fentanil. Os resultados enfatizam que feniramina é um medicamento conveniente para diminuir essa tosse.

Mastocitosis cutánea: reporte de un caso / Cutaneous mastocytosis: A case report

Introducción La mastocitosis representa un grupo de enfermedades caracterizadas por una acumulación excesiva de mastocitos en uno o múltiples tejidos. Puede limitarse a la piel o tener un compromiso sistémico, siendo de baja prevalencia y pronóstico benigno en la infancia. Objetivo Reportar un caso de urticaria pigmentosa como subtipo de mastocitosis cutánea y hacer una revisión bibliográfica enfocada en los hallazgos clínicos, el diagnóstico y el manejo inicial básico. Caso clínico Lactante de 6 meses de edad con múltiples máculas y pápulas de color café claro localizadas en el tronco, los brazos y las piernas, cuadro compatible con una urticaria pigmentosa, confirmada mediante biopsia. Se solicitaron exámenes para descartar compromiso sistémico. La paciente fue tratada con medidas generales, educación y antihistamínicos, con excelente evolución. Conclusiones La mastocitosis cutánea es una enfermedad poco común, de buen pronóstico. En la infancia generalmente bastan las medidas generales y educación para obtener resultados favorables. La terapia farmacológica de primera línea son los antagonistas H1.

Introduction Mastocytosis represents a group of diseases characterised by an excesive accumulation of mastocytes in one or multiple tissues. It can affect only the skin, or have a systemic involvement. It has a low prevalence, and the prognosis is benign in children. Objective To report a case of urticaria pigmentosa as a subtype of cutaneous mastocytosis, and present a literature review focused on clinical findings, diagnosis and initial basic management. Clinical case A child of six months of age presenting with multiple blemishes and light brown papules located on the trunk, arms and legs. The symptoms were compatible with urticaria pigmentosa, and was confirmed by biopsy. Tests to rule out systemic involvement were requested. The patient was treated with general measures, education, and antihistamines, with favourable results. Conclusions Cutaneous mastocytosis is a rare disease with a good prognosis. In childhood general measures and education are usually enough to obtain favourable results. Histamine H1 antagonists are the first line drug treatment.

Anaphylaxis audit in a busy metropolitan Emergency Department: a review of real life management compared to best practice

BACKGROUND: Deficiencies in anaphylaxis management in Emergency Departments is well recognised despite established guidelines for its treatment. OBJECTIVE: To identify deficiencies in the management of anaphylaxis in a busy metropolitan Emergency Department and determine if an education intervention could correct these. METHODS: Paediatric and adult admissions to the Emergency Department of a busy hospital were tracked over a 10-month period with a targeted educational program being instituted at 5 months. The electronic records were retrospectively reviewed looking for cases of anaphylaxis and milder forms of immediate type allergic reactions presenting with a combination of urticaria and nonairway threatening angioedema. Anaphylaxis presentation was graded using the Brown grading system. Use of all medication during resuscitation was documented. Observation period before discharge and referral to specialist unit for follow-up was noted. RESULTS: In the first 5 months, 38 patients fulfilled our criteria. Three had severe anaphylaxis, 13 had moderately severe anaphylaxis and 12 had urticaria and angioedema without anaphylaxis. Anaphylaxis was not always recognised or graded leading to inappropriate management with adrenaline often being withheld. Promethazine, usually given in parenteral form, was frequently administered. Observation time was often inadequate. Referral to an immunologist was not universally followed through. Following the educational intervention 58 patients fulfilled our criteria over the next 5 months. The appropriate use of adrenaline increased by 21% and the use of sedating antihistamines decreased by 16%, while the number of referrals to an immunologist increased by 24%. There was an 11% reduction in the number of patients who were observed for at least 4 hours. CONCLUSION: A number of deficiencies in the management of anaphylaxis presentations have been identified. Targeted educational activities aimed at the Emergency Department hospital staff may improve outcomes.

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.

Gynecomastia induced by H1-antihistamine (ebastine) in a patient with idiopathic anaphylaxis

H1-antihistamine is generally a well-tolerated and safe drug. However, in resemblance with all other drugs, H1-antihistamines can also prompt adverse drug reactions (ADRs). We recently encountered the very unusual ADR of H1-antihistamine-induced gynecomastia. A 21-year-old man with idiopathic anaphylaxis was treated with ebastine (Ebastel), a second-generation H1-antihistamine, for the prevention of anaphylaxis. Three months later, the patient remained well without anaphylaxis, but had newly developed gynecomastia. Because anaphylaxis recurred after the cessation of H1-antihistamine, the preventive medication was changed to omalizumab. A few months later, his gynecomastia had entirely disappeared. Physicians should be aware of this exceptional ADR of H1-antihistamine.

Clinical study of the combination therapy with intranasal antihistamine and nasal corticosteroids in the treatment of nasal obstruction of persistent non-allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To determine if greater efficacy could be achieved with the intranasal antihistamine azelastine and the intranasal corticosteroid fluticasone propionate used concurrently in the treatment of nasal obstruction of persistent non-allergic rhinitis.@*METHOD@#A total of 162 persistent non-allergic rhinitis cases with moderate to severe nasal obstruction were randomized to treatment with the following: the combination therapy or nasal corticosteroids monotherapy. Efficacy was assessed by change from baseline in nasal obstruction score at week 2 and week 6 visits. The perceptions of global treatment satisfaction(convenience, side effects, cost and effectiveness) in both groups were analyzed.@*RESULT@#In both groups, the nasal obstruction score assessment descended significantly at week 2 and week 6 visits versus at baseline (all P < 0.01). At week 2 and week 6 visits, the nasal obstruction score in the combination therapy groups were significantly improved than that in nasal corticosteroids monotherapy groups (all P < 0.01). The perceptions of global treatment satisfaction in the combination therapy groups were significantly better (P < 0.05).@*CONCLUSION@#Azelastine nasal spray and intranasal corticosteroid in combination may provide a substantial therapeutic benefit for patients with persistent non-allergic rhinitis, especially nasal obstruction. The combination therapy was well tolerated and safety.