Osteonecrosis múltiple inducida por glucocorticoides / Multiple osteonecrosis induced bye glucocorticoids / Osteonecrose múltipla induzida por glicocorticóides

La osteonecrosis múltiple es una entidad poco frecuente que se define por el compromiso de al menos tres regiones diferentes. Es indispensable el abordaje multidisciplinario de los pacientes que la padecen tanto para el diagnóstico como el tratamiento oportuno. Presentamos el caso clínico de un paciente joven que presenta una osteonecrosis múltiple con compromiso de ambas caderas, hombros, rodillas, codo derecho y cuello de pie izquierdo. El principal factor de riesgo presente en nuestro caso es el consumo de glucocorticoides.

Multiple osteonecrosis is a rare entity that is defined by the involvement of at least three different regions. A multidisciplinary approach to patients who suffer from it is essential for both diagnosis and timely treatment. We present the clinical case of a young patient who presented multiple osteonecrosis with involvement of both hips, shoulders, knees, right elbow, and neck of the left foot. The main risk factor present in our case is the consumption of glucocorticoids.

A osteonecrose múltipla é uma entidade rara que se define pelo envolvimento de pelo menos três regiões diferentes. Uma abordagem multidisciplinar aos pacientes que sofrem com isso é essencial para o diagnóstico e tratamento oportuno. Apresentamos o caso clínico de um paciente jovem que apresenta osteonecrose múltipla envolvendo quadris, ombros, joelhos, cotovelo direito e pescoço do pé esquerdo. O principal fator de risco presente no nosso caso é o consumo de glicocorticóides.

Bitter kola and kola nut use and their effect on treatment outcome on People Living with HIV at a Military Hospital in Benue state Nigeria: Bitter kola (Garcinia) and Cola nut (Cola nitida among PLWHIV

Introduction Bitter Kola (Garcinia Kola) and kola nut, contains substances attributed to numerous effects on humans including anti-inflammatory, anti-allergic properties, anti-infective and caffeinism. This study explores Bitter kola and kola nut use and its impact on treatment outcome on People Living with HIV (PLWHIV). Methods: The study was conducted at a Military Hospital in Nigeria. An analytical cross-sectional study was done using questionnaire among 700 HIV-positive clients selected using simple random sampling. Data were collected by researcher and three trained assistants. Chi-square test and binary logistic regression were used for identifying associations and predictors, respectively. The level of significance was set at p < 0.05. Results: Findings show that 260 (63.6%) and 179 (25.6%) have ever and currently used Bitter kola/Kola nut, respectively. Also, 14 (7.8%) used Bitter kola/Kola nut alone while 165 (92.2%) used it in addition to other substances, especially with alcohol 123 (68.7%). Bitter kola use was associated with age (p = 0.037), gender (p < 0.001), occupation (p = 0.001), and number of children (p < 0.011). Identified predictors were being a female (AOR 0.79; 95% CI 0.08-0.92) and earning <18,000 Naira (AOR 2.91; 95% CI 2.03-21.54). There was no association of Bitter kola/kola nut use with CD4 count and viral load suppression. Conclusion: Though Kola nut and Bitter kola use was high as in the general population we have not found any effect on treatment outcome among PLWHIV. This calls for more research to ascertain if there are other possible beneficial effects on PLWHIV.

Anti-pseudo-allergic components in licorice extract inhibit mast cell degranulation and calcium influx / 中国天然药物

Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.

Effect of topical corticosteroids on nasal patency after acute positive airway pressure exposure / Efeito dos corticosteroides tópicos na patência nasal após exposição aguda à pressão positiva nas vias aéreas

Abstract Introduction Nasal congestion and obstruction are reported in the majority of continuous positive airway pressure users and are frequently cited as reasons for noncompliance. Baseline inflammation due to allergic rhinitis could increase or exacerbate the inflammatory effect of high airflow in the nasal cavity as the result of continuous positive airway pressure and lead to greater continuous positive airway pressure intolerance. In this setting, intranasal steroids would be expected to counteract the nasal inflammation caused by allergic rhinitis and/or continuous positive airway pressure. Objective The aim of the present study is to evaluate the effects of topical corticosteroid use on nasal patency after acute exposure to positive pressure. Methods Ten individuals with allergic rhinitis were exposed to 1 h of continuous airway pressure (15 cm H2O) in the nasal cavity, delivered by a continuous positive airway pressure device. Visual analog scale, nasal obstruction symptom evaluation scale, acoustic rhinometry and peak nasal inspiratory flow were performed before and after the intervention. After 4 weeks topical nasal steroid (budesonide) application, positive pressure exposure was repeated as well as the first assessments. Results Patients reported a statistically significant improvement both on the visual analog (p = 0.013) and obstruction symptom evaluation scales (p < 0.01). Furthermore, objective measurements were improved as well, with increased nasal cavity volume on acoustic rhinometry (p = 0.02) and increased peak nasal inspiratory flow (p = 0.012), after corticosteroid treatment. Conclusion In patients with allergic rhinitis, intranasal corticosteroid therapy improved objective and subjective parameters of nasal patency after acute exposure of the nasal cavity to positive pressure.

Resumo Introdução Congestão e obstrução nasais são relatadas na maioria dos usuários de pressão positiva contínua nas vias aéreas e são frequentemente mencionadas como razões para a falta de aderência. A inflamação basal devida à rinite alérgica pode aumentar ou agravar o efeito inflamatório do alto fluxo de ar na cavidade nasal como resultado da pressão positiva contínua nas vias aéreas e aumentar a intolerância à mesma. Nesse cenário, espera-se que os esteróides intranasais neutralizem a inflamação nasal causada pela rinite alérgica e/ou pela pressão positiva contínua nas vias aéreas. Objetivo Avaliar os efeitos do uso tópico de corticosteroides na patência nasal após exposição aguda à pressão positiva. Métodos Dez indivíduos com rinite alérgica foram expostos a uma hora de pressão contínua nas vias aéreas (15 cm H2O) na cavidade nasal, fornecida por um dispositivo de pressão positiva contínua nas vias aéreas. A escala visual analógica, a escala Nasal Obstruction Symptom Evaluation, rinometria acústica e pico de fluxo inspiratório nasal foram aplicados antes e após a intervenção. Após 4 semanas de aplicação tópica de esteroide nasal (budesonida), a exposição positiva à pressão foi repetida, bem como as primeiras avaliações. Resultados Os pacientes relataram uma melhoria estatisticamente significante tanto na escala visual analógica (p = 0,013) quanto na escala Nasal Obstruction Symptom Evaluation (p < 0,01). Além disso, as medidas objetivas também foram melhoradas, com aumento do volume da cavidade nasal na rinometria acústica (p = 0,02) e aumento do pico de fluxo inspiratório nasal (p = 0,012), após o tratamento com corticosteroide. Conclusão Em pacientes com rinite alérgica, a terapia com corticosteroide intranasal melhorou os parâmetros objetivos e subjetivos da patência nasal após exposição aguda da cavidade nasal à pressão positiva.

Topical corticosteroid induced ulcerated striae

Abstract We report four cases of ulcerated striae following misuse of fixed dose combinations creams containing clobetasol propionate with antifungal and antibacterial agents.

Tratamento da asma: o que podemos aprender com um médico do século XVI / Asthma treatment: what we can learn from a 16th-century physician

Girolamo Cardano, médico italiano do Renascimento, descreveu em suas memórias o tratamento detalhado de um arcebispo escocês que apresentava, havia mais de 10 anos, um quadro de asma grave. O tratamento, sem paralelo na história da Medicina até então, foi um verdadeiro sucesso, ajudando a firmar o nome de Cardano como um dos mais lidos e admirados personagens dos séculos XVI e XVII. Uma possível interpretação para a melhora significativa apresentada pelo paciente seria a resposta a uma medida de higiene ambiental antialérgica: a retirada do quarto de todo material que contivesse penas (colchão, mantas e travesseiros). No entanto, a análise detalhada do relato (excluindo-se a terapia medicamentosa, por não ter nenhum respaldo científico), faz surgir uma nova interpretação, pois a reeducação comportamental implementada foi surpreendente. Muitas das medidas defendidas por Cardano foram inovadoras para a época e, curiosamente, encontram ressonância na Hipótese da Biodiversidade, a mais recente tentativa de explicar a escalada da alergia e das doenças inflamatórias a partir de meados do século XX. A perseguição pela Inquisição, associada às críticas de irreligiosidade e possível retrocesso em sua capacidade mental, provavelmente impediram que o médico italiano fosse lembrado nos dias de hoje. O caso descrito nos relembra, em um momento de afã por novas medicações para asma, junto a tempos exageradamente curtos de consulta, que as medidas de orientação e educação podem ter um impacto significativo, chegando mesmo a se equiparar à terapêutica medicamentosa.

Girolamo Cardano, an Italian physician of the Renaissance, described in his memoirs the detailed treatment of a Scottish archbishop who had had severe asthma for more than 10 years. The treatment, unparalleled in the history of Medicine until then, was truly successful, helping to establish the name of Cardano as one of the most read and admired characters of the 16th and 17th centuries. A possible interpretation for the significant improvement presented by the patient is the response to an anti-allergic environmental hygiene measure: removing from the room all material containing feathers (mattress, comforters, and pillows). However, a detailed analysis of the report (excluding the drug therapy, which has no scientific support) gives rise to a new interpretation, as the implemented behavioral re-education measure was surprising. Many of the measures advocated by Cardano were innovative for the time and, interestingly, find resonance in the Biodiversity Hypothesis, the most recent attempt to explain the escalation of allergy and inflammatory diseases initiating in the mid-20th century. Persecution by the Inquisition, associated with criticisms of irreligiousness and possible retrogression in his mental capacity, probably prevented the Italian physician from being remembered today. The described case reminds us, in a moment of anxiety for new asthma medications, together with exaggeratedly short consultation times, that guidance and education measures can have a significant impact, possibly reaching the same level as drug therapy.

Individualized treatment for allergic rhinitis based on key nasal clinical manifestations combined with histamine and leukotriene D4 levels / Tratamento individualizado para a rinite alérgica baseado nas principais manifestações clínicas nasais e dos níveis de histamina e leucotrieno D4

Abstract Introduction The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity. Objective To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies. Methods A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors. Results Loratadine + mometasone furoate and loratadine + mometasone furoate + montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p < 0.05). Meanwhile, montelukast + mometasone furoate and montelukast + mometasone furoate + loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p < 0.05). Conclusion Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.

Resumo Introdução A rinite alérgica é basicamente classificada de acordo com os antígenos causadores, tipos de doença, peridiocidade e gravidade dos sintomas. Objetivo Avaliar os tipos clínicos e a abordagem terapêutica individualizada para cada tipo de rinite alérgica e determinar o método de tratamento ideal utilizando várias terapias de combinação de fármacos. Método Um total de 108 participantes com rinite alérgica foram divididos em três grupos com base nos sintomas. Posteriormente, cada grupo foi subsequentemente categorizado em quatro subgrupos com base nos medicamentos recebidos. A eficácia dos tratamentos foi avaliada utilizando os escores da escala visual analógica EVA dos sintomas nasais totais e individualmente, índice de declínio do escore de sintomas, níveis de histamina e leucotrienos e níveis de expressão de mRNA e proteína dos receptores de histamina 1 e cisteinil-leucotrieno 1. Resultados As associações entre loratadina + furoato de mometasona, assim como a de loratadina + furoato de mometasona + montelucaste melhoraram significativamente o sintoma de espirros e reduziram os níveis de histamina em comparação às outras terapias combinadas (p < 0,05). Por outro lado, a associação montelucaste + furoato de mometasona, assim como a associação montelucaste + furoato de mometasone + loratadina melhoraram consideravelmente o sintoma de obstrução nasal e diminuíram os níveis de leucotrieno D4 em comparação com as outras combinações (p < 0,05). Conclusão A avaliação clínica dos sintomas combinada com a detecção experimental dos níveis de histamina e leucotrieno pode ser um método objetivo e preciso para classificar clinicamente os tipos de rinite alérgica. Além disso, o tratamento individualizado baseado na classificação da rinite alérgica pode resultar no aumento da eficácia do tratamento.

Crusted (Norwegian) scabies in an infant: A case report

@#INTRODUCTION: Norwegian or crusted scabies is a rare and highly contagious form of skin parasitosis caused by Sarcoptes scabiei var. hominis. Individuals maffffinly affected are considered to be immunocompromised such as those on prolonged glucocorticosteroid therapy, with AIDS or organ transplant patients. This disease presents as a hyperkeratotic dermatosis with an acral distribution. CASE REPORT: This is a case of a 2-month-old healthy Filipino male, who was previously managed as a case of miliaria rubra and treated with clobetasol 0.05% – ketoconazole 2% cream for 1 week. The papules and plaques became widespread. Consult with a pediatrician revealed widespread scabies and for which patient was prescribed topical permethrin with no improvement. On examination, patient presented with multiple erythematous papules and plaques with crusts on the face, trunk, extremities, palms and soles. Thickened yellowish plaques were observed on the palms and soles. Both parents also presented with widespread papules most prominent on the flexural areas accompanied by nocturnal pruritus. On dermoscopy, numerous mites and burrows were seen in a “jet with contrail pattern.” Prominent yellowish scales were also noted. Patient was admitted due to fever and superimposed bacterial infection and was given IV oxacillin, paracetamol, 8% precipitated sulfur in a hypoallergenic lotion applied twice daily and sodium fusidate ointment. On the 4th hospital day, the patient was afebrile and the lesions were noted to decrease in both erythema and crusting. Follow-up dermoscopy revealed absence scales, burrows and mites. CONCLUSION: Prolonged, unsupervised use of topical corticosteroids in our case most likely induced an immunocompromised state thus predisposing the patient to develop Norwegian scabies. In countries were cases of Norwegian scabies have been unresponsive to permethrin and when ivermectin is not available, the use of precipitated sulfur may still be the best therapeutic and safest option for infants.

The efficacy and safety of ciclesonide for the treatment of perennial allergic rhinitis: a systematic review and meta-analysis / Eficácia e segurança da ciclesonida no tratamento da rinite alérgica perene: uma revisão sistemática e metanálise

Abstract Introduction: Allergic rhinitis is a chronic inflammatory disease which affects 1 out of 6 individuals. Perennial allergic rhinitis accounts for 40% of AR cases. Ciclesonide is one of the relatively new intranasal steroid for allergic rhinitis. Objective: The purpose of this study was to evaluate the efficacy and safety of ciclesonide in the treatment of perennial allergic rhinitis. Methods: We searched Pubmed, Scientific Citation Index, Embase, Clinical Trial Registries for randomized controlled trials and Cochrane Central Register of Controlled Trials to find out the randomized controlled Trial comparing ciclesonide with placebo for PAR. Results: Eight studies were included. In comparison with placebo groups, ciclesonide groups significantly decreased Reflective Total Nasal Symptom Score (MD = −0.56; 95% CI −0.72 to 0.39, p < 0.00001) with heterogeneity (p = 0.19, I2 = 24%), Instantaneous Total Nasal Symptom Score (MD = −0.57; 95% CI −0.75 to −0.39, p < 0.00001) with heterogeneity (p = 0.34, I2 = 11%). A significant effect for Reflective Nasal Symptom Score Subtotal (MD = −0.15; 95% CI −0.18 to −0.13, p < 0.00001) with heterogeneity (p = 0.12, I2 = 24%) was also demonstrated. Rhinoconjunctivitis quality of life questionnaire score (RQLQs) (MD = −0.27; 95% CI −0.39 to −0.15, p < 0.00001) with heterogeneity (p = 0.58, I 2 = 0%) in the treatment of ciclesonide was also significantly reduced. In addition, the difference in Treatment-Emergent Adverse Events between the two groups was not significant. Conclusion: Ciclesonide can improve perennial allergic rhinitis without increasing adverse events. Ciclesonide may be another valuable choice for perennial allergic rhinitis in the future.

Resumo Introdução: A rinite alérgica é uma doença inflamatória crônica que afeta um a cada seis indivíduos. A rinite alérgica perene é responsável por 40% dos casos de rinite alérgica. A ciclesonida é um dos corticosteroides intranasais mais novos para o tratamento dessa condição clínica. Objetivo: Avaliar a eficácia e segurança da ciclesonida no tratamento da rinite alérgica perene. Método: Uma busca foi feita nos bancos de dados Pubmed, Scientific Citation Index, Embase e Clinical Trial Registries por ensaios clínicos randomizados e Cochrane Central Register of Controlled Trials por estudos controlados randomizados que comparassem ciclesonida com placebo no tratamento da rinite alérgica perene. Resultados: Oito estudos foram incluídos. Em comparação com os grupos placebo, os grupos ciclesonida mostraram diminuição significante no escore do Reflective Total Nasal Symptom Score (DM = −0,56; IC 95%: −0,72 a −0,39, p < 0,00001) com heterogeneidade (p = 0,19, I2 = 24%), do Instantaneous Total Nasal Symptom Score (DM = −0,57; IC95%: −0,75 a −0,39, p < 0,00001) com heterogeneidade (p = 0,34, I2 = 11%). Um efeito significante no escore do Reflective Nasal Symptom Score Subtotal (DM = −0,15; IC 95%: −0,18 a −0,13, p < 0,00001) com heterogeneidade (p = 0,12, I2 = 24%) também foi demonstrado. O escore do Rhinoconjunctivitis Quality of Life Questionnaire score (RQLQs) (DM = −0,27; IC 95%: −0,39 a −0,15, p < 0,00001) com heterogeneidade (p = 0,58, I2 = 0%) também foi significantemente reduzido no tratamento com ciclesonida. Além disso, a diferença em relação aos eventos adversos emergentes do tratamento entre os dois grupos não foi significante. Conclusão: A ciclesonida pode melhorar a rinite alérgica perene sem aumentar os eventos adversos. Esse fármaco pode ser outra opção valiosa para a rinite alérgica perene no futuro.

Incapacitating solar urticaria: successful treatment with omalizumab

Abstract: Solar urticaria is a rare form of physical urticaria mediated by immunoglobulin E. The lesions appear immediately after the sun exposure, interfering with the patient's normal daily life. Omalizumab, a monoclonal anti-IgE antibody, has been recently approved for the treatment of chronic spontaneous urticaria, and the latest reports support its role also in the treatment of solar urticaria. Hereby, we report a case of solar urticaria refractory to conventional treatment strategies, with an excellent response to treatment with omalizumab and phototesting normalization.

Consensus on the diagnostic and therapeutic management of chronic spontaneous urticaria in adults - Brazilian Society of Dermatology

Abstract: Background: Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous. Objectives: To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US). Methods: A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults. Results: Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence). Conclusions: Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.

Therapeutic Effect of Glucosamine on an Atopic Dermatitis Animal Model

BACKGROUND: Recent studies have reported that glucosamine (GlcN) showed therapeutic effects in allergic diseases such as asthma and rhinitis, and its mechanisms include the suppression of T helper type 2 immune responses and the nuclear factor-κB pathway. OBJECTIVE: We aimed to investigate the effect of GlcN on atopic dermatitis (AD) in an animal model. METHODS: Twenty-five BALB/c mice were divided into five groups (groups A~E). Group A was the phosphate-buffered saline (PBS)-treated group without AD induction. Group B was the PBS control group with AD induction. Groups C to E were the AD induction groups, which were treated with three different doses of GlcN (10 mg, 20 mg, and 40 mg, respectively). Histopathological examination was performed after GlcN administration. Interleukin (IL)-4, IL-13, and IL-17 cytokine levels were measured by enzyme-linked immunosorbent assay using skin biopsy specimens. Serum total immunoglobulin E (IgE) concentrations were measured before and after administration with GlcN or PBS. RESULTS: Clinical dermatitis scores decreased with increasing GlcN dose (p<0.001). Concentrations of tissue IL-13 and IL-17 decreased after GlcN administration (each group: p=0.002 and p<0.001, respectively), but the concentrations of tissue IL-4 did not show differences across groups. Serum IgE levels tended to be lower after GlcN administration (p=0.004). Histopathological scores were not significantly different among groups B~E (p=0.394). CONCLUSION: GlcN improved AD symptoms and decreased tissue IL-13, IL-17, and serum total IgE levels in an animal model.

Intranasal Treatment With 1, 25-Dihydroxyvitamin D3 Alleviates Allergic Rhinitis Symptoms in a Mouse Model

PURPOSE: Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear. METHODS: The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay. RESULTS: In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased. CONCLUSIONS: The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.

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.

Omalizumab para la rinosinusitis crónica / Omalizumab for chronic rhinosinusitis

Resumen INTRODUCCIÓN: La rinosinusitis crónica es una enfermedad inflamatoria crónica de alta prevalencia que compromete la mucosa de la cavidad nasal y senos paranasales. La inmunoglobulina E es un mediador inflamatorio que juega un rol etiopatogénico en esta condición, por lo que se ha planteado que omalizumab, un anticuerpo monoclonal anti-inmunoglobulina E, podría constituir una alternativa de tratamiento. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cinco revisiones sistemáticas que en conjunto incluyeron cinco estudios primarios, de los cuales dos corresponden a ensayos controlados aleatorizados. Concluimos que en pacientes con rinosinusitis crónica, no está claro si omalizumab lleva a una mejoría en la escala de pólipos nasales, la calidad de vida, el bienestar general o los síntomas nasales porque la certeza de la evidencia es muy baja. Por otra parte, el uso de omalizumab probablemente se asocia a efectos adversos frecuentes.

Abstract INTRODUCTION: Chronic rhinosinusitis is a high prevalence chronic inflammatory disease that involves nasal mucosa and paranasal sinuses. Immunoglobulin E is an inflammatory mediator that plays an etiopathogenic role in this condition, so omalizumab, an anti-immunoglobulin E monoclonal antibody, might be a therapeutic alternative. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified five systematic reviews that included five primary studies overall, of which two correspond to randomized trials. We concluded it is not clear whether omalizumab leads to an improvement in the nasal polyps scale, quality of life, general well-being or nasal symptoms in patients with chronic rhinosinusitis, because the certainty of the evidence is very low. On the other hand, omalizumab is probably associated with frequent adverse effects.

Immediate Hypersensitivity Reactions Induced by Triamcinolone in a Patient with Atopic Dermatitis

Corticosteroids are potent anti-inflammatory and anti-allergic agents used in the treatment of various inflammatory diseases, including allergic disease. They are frequently considered the therapy-of-choice for many skin diseases. However, allergic reactions caused by corticosteroids have been reported. Among these, delayed reactions to topical steroids are more common, whereas immediate reactions to systemic steroids are rare. Herein, we report the case of a 32-year-old woman with triamcinolone-induced immediate hypersensitivity reaction, in which the patient had a positive prick test result with triamcinolone. She has had atopic dermatitis (AD) for three years. She had used systemic steroid, cyclosporine, and antihistamine with topical steroids for AD. In clinic, approximately 10 minutes after intralesional injection of triamcinolone, she complained of erythematous patches with slight elevation and itching on the face, trunk, and both hands. After intravenous injection of dexamethasone, her symptoms got worse. After treatment with epinephrine, all symptoms resolved within two hours. We performed an open test and skin prick test. She had a positive result only from the prick test with triamcinolone; all other steroids showed negative results from the open tests. Dermatologists should be aware of the possibility of anaphylaxis or other allergic hypersensitivity in response to corticosteroids.

Pharmacokinetics and safety of repirinast tablets in healthy Chinese subjects

ABSTRACT Repirinast is a new, synthetic, disodium cromoglycate-like antiallergic agent for oral administration in humans. This study evaluated the safety, tolerability and pharmacokinetics of repirinast tablets in healthy Chinese volunteers. This was a phase I, open-label, randomized, single- and multiple-dose study. Subjects were assigned to receive a single dose of repirinast tablet at either 150, 300, or 450 mg, or multiple doses of 150 mg twice daily for 5 days. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of active metabolite MY-1250 (deesterified repirinast) were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 0.75 hour, and the mean t1/2 was approximately 16.21 hours. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 150 to 450 mg. In the multiple-dose study, the steady-state was reached within 3 days with no accumulation. Repirinast tablet was well tolerated in healthy Chinese subjects.