Distúrbios do olfato, uma revisão narrativa do diagnóstico ao tratamento / Olfactory dysfunction: a narrative review from diagnosis to treatment

Os distúrbios do olfato (DO) impactam de forma significativa na qualidade de vida dos indivíduos, e o conhecimento teórico a respeito do assunto deve ser de domínio dos alergologistas e imunologistas clínicos, possibilitando, assim, o seu diagnóstico e implementação de intervenções. Suas causas podem ser variadas, entre elas estão: rinite alérgica, rinossinusite crônica com ou sem pólipos, infecções de vias aéreas superiores, exposição a substâncias químicas, doenças neurológicas, drogas, traumas e o próprio envelhecimento. O olfato pode ser avaliado e mensurado através de testes com metodologias diferentes, cujo objetivo é avaliar parâmetros como a identificação de odores, limiar e discriminação olfativa. Esses testes são de fundamental importância para caracterizar objetivamente a queixa do paciente, como também avaliar o olfato antes e após determinada aplicação terapêutica. O tratamento das desordens olfativas é baseado em sua etiologia, portanto determinar a sua causa é indispensável para uma melhor eficácia no manejo. Entre as principais opções estão os corticoides tópicos, com impacto significativo nos pacientes com doença sinusal associada, treinamento olfatório e outras intervenções como ômega 3, vitamina A intranasal, e terapias que ainda requerem mais estudos.

Olfactory dysfunction significantly impacts quality of life, and allergists and clinical immunologists must be informed about it for diagnostic and interventional purposes. The causes are varied: allergic rhinitis, chronic rhinosinusitis with or without polyps, upper airway infections, exposure to chemicals, neurological diseases, drugs, trauma, and aging itself. Olfactory function can be evaluated and measured by several tests that use different methodologies to evaluate and identify odors, olfactory threshold, and olfactory discrimination. These tests are fundamental for objectively characterizing patient complaints and evaluating olfactory function before and after therapeutic interventions. Olfactory disorders are treated according to their etiology, so determining their cause is a major factor in treatment efficacy. The main options include topical corticosteroids, which have a significant impact on patients with sinus disease, olfactory training, other therapies (such as omega 3 and intranasal vitamin A), in addition to therapies that require further research.

IgE and IgG4 Epitopes of Dermatophagoides and Blomia Allergens before and after Sublingual Immunotherapy.

Sublingual immunotherapy (SLIT) is used worldwide to treat house dust mites (HDM) allergy. Epitope specific immunotherapy with peptide vaccines is used far less, but it is of great interest in the treatment of allergic reactions, as it precludes the drawbacks of allergen extracts. The ideal peptide candidates would bind to IgG, blocking IgE-binding. To better elucidate IgE and IgG4 epitope profiles during SLIT, sequences of main allergens, Der p 1, 2, 5, 7, 10, 23 and Blo t 5, 6, 12, 13, were included in a 15-mer peptide microarray and tested against pooled sera from 10 patients pre- and post-1-year SLIT. All allergens were recognized to some extent by at least one antibody isotype and peptide diversity was higher post-1-year SLIT for both antibodies. IgE recognition diversity varied among allergens and timepoints without a clear tendency. Der p 10, a minor allergen in temperate regions, was the molecule with more IgE-peptides and might be a major allergen in populations highly exposed to helminths and cockroaches, such as Brazil. SLIT-induced IgG4 epitopes were directed against several, but not all, IgE-binding regions. We selected a set of peptides that recognized only IgG4 or were able to induce increased ratios of IgG4:IgE after one year of treatment and might be potential targets for vaccines.

In-vitro NLRP3 functional test assists the diagnosis of cryopyrin-associated periodic syndrome (CAPS) patients: A Brazilian cooperation.

OBJECTIVE: To report our five-years experience on the use of NLRP3 inflammasome functional assays in the differential diagnosis of Brazilian patients with a clinical suspicion of CAPS. PATIENTS AND METHODS: The study included 9 patients belonging to 2 families (I, II) and 7 unrelated patients with a clinical suspicion of AID according to Eurofever/PRINTO classification, recruited between 2017 and 2022. The control group for the NLRP3 functional assay consisted of 10 healthy donors and for the CBA cytokines measurement of 19 healthy controls. Patients underwent clinical evaluation, genetic and functional analysis. RESULTS: All members of the family I received the diagnosis of Muckle-Wells Syndrome (MWS), carried the NLRP3 Thr348Met variant and resulted positive for the functional assay. The 2 patients of the family II resulted negative for the mutational screening but positive for the functional assay compatible with a MWS clinical phenotype. In 2 unrelated patients with NLRP3 mutations, including a novel mutation (Gly309Val, Asp303His), a positive functional test confirmed the clinical diagnosis of NOMID. 3 unrelated MWS and 1 FCAS patients resulted negative to the genetic screening and positive for the functional test. One patient with a FCAS-like phenotype harbored the NLRP12 His304Tyr variant confirming the diagnosis of FCAS2. CONCLUSION: The NLRP3 inflammasome functional assay can assist the clinical diagnosis of CAPS even in patients with unknown genetic defects.

Recessive NLRC4-Autoinflammatory Disease Reveals an Ulcerative Colitis Locus.

PURPOSE: NLRC4-associated autoinflammatory disease (NLRC4-AID) is an autosomal dominant condition presenting with a range of clinical manifestations which can include macrophage activation syndrome (MAS) and severe enterocolitis. We now report the first homozygous mutation in NLRC4 (c.478G > A, p.A160T) causing autoinflammatory disease with immune dysregulation and find that heterozygous carriers in the general population are at increased risk of developing ulcerative colitis. METHODS: Circulating immune cells and inflammatory markers were profiled and historical clinical data interrogated. DNA was extracted and sequenced using standard procedures. Inflammasome activation assays for ASC speck formation, pyroptosis, and IL-1ß/IL-18 secretion confirmed pathogenicity of the mutation in vitro. Genome-wide association of NLRC4 (A160T) with ulcerative colitis was examined using data from the IBD exomes portal. RESULTS: A 60-year-old Brazilian female patient was evaluated for recurrent episodes of systemic inflammation from six months of age. Episodes were characterized by recurrent low-grade fever, chills, oral ulceration, uveitis, arthralgia, and abdominal pain, followed by diarrhea with mucus and variable skin rash. High doses of corticosteroids were somewhat effective in controlling disease and anti-IL-1ß therapy partially controlled symptoms. While on treatment, serum IL-1ß and IL-18 levels remained elevated. Genetic investigations identified a homozygous mutation in NLRC4 (A160T), inherited in a recessive fashion. Increased ASC speck formation and IL-1ß/IL-18 secretion confirmed pathogenicity when NLRC4 (A160T) was analyzed in human cell lines. This allele is significantly enriched in patients with ulcerative colitis: OR 2.546 (95% 1.778-3.644), P = 0.01305. CONCLUSION: NLRC4 (A160T) can either cause recessively inherited autoinflammation and immune dysregulation, or function as a heterozygous risk factor for the development of ulcerative colitis.

O estado da arte das síndromes autoinflamatórias associadas à criopirina / The state of the art of cryopyrin-associated periodic syndromes

As síndromes autoinflamatórias associadas à criopirina (CAPS) compreendem um grupo espectral de doenças raras autoinflamatórias. Todas estas doenças estão relacionadas ao inflamassoma NLRP3, sendo que de 50-60% dos pacientes apresentam mutações ao longo do gene NLRP3. Clinicamente, febre recorrente associada à urticária neutrofílica e outros sintomas sistêmicos são o grande marco clínico, comum a todo o espectro. O bloqueio da interleucina-1 trouxe grande alívio ao tratamento destas desordens, mas variações na resposta clínica podem ser observadas, principalmente nos espectros mais graves. Neste trabalho os autores trazem uma revisão do estado da arte das doenças autoinflamatórias CAPS. Foi realizado levantamento de literatura e, ao final, 49 artigos restaram como base para construção do texto final. O trabalho traz de forma narrativa os principais pontos relacionados a imunofisiopatologia, manifestação clínica, diagnóstico, tratamento, complicações e novas armas diagnósticas, e terapia gênica.

Cryopyrin-associated periodic syndromes (CAPS) comprise a spectrum of rare autoinflammatory disorders. They are all related to the NLRP3 inflammasome, and 50-60% of the patients harbor mutations along the NLRP3 gene. Clinically, recurrent fever associated with neutrophilic urticaria and other systemic symptoms are a hallmark of all the disorders in the spectrum. Biologic drugs that can block interleukin-1 were a milestone for the treatment of such rare diseases, although variability in clinical response to this therapeutic intervention were observed, especially in those affected by severe phenotypes. In this paper, the authors provide a state-of-the-art review of CAPS. A literature search was performed and, finally, 49 articles remained for the construction of the final manuscript. The article presents a narrative review focused on the topics related to immune pathophysiology, clinical manifestations, diagnosis, treatment, complications and new therapeutic options, and gene therapy.

Immunological repertoire linked to PSTPIP1-associated myeloid-related inflammatory (PAMI) syndrome.

BACKGROUND: Mutations along PSTPIP1 gene are associated to two specific conditions, PAPA syndrome and PAMI syndrome, both autoinflammatory disorders associated to disturbances in cytoskeleton formation. Immunological aspects of PAMI syndrome has not yet been reported neither the clinical impact on therapeutical decisions. METHODS: Clinical data of patients records were retrospectively accessed. Genomic DNA were extracted and sequenced following standard procedures. Peripheral lymphocytes were quantified in T, B e FOXP3 phenotypes. RESULTS: We describe two related patients with PAMI syndrome harboring the usual E250K mutation. Anti-IL1 therapy could partially control the disease in the index patient. A broad spectrum of immunological effects as well as an aberrant expression of FOXP3 could be observed. CONCLUSIONS: Here we report two related brazilian patients with PAMI syndromes harboring the E250K mutation in PSTPIP1, their immunological aspects and the therapeutical response to canakinumab.

Mathematical modeling of the transmission of SARS-CoV-2-Evaluating the impact of isolation in São Paulo State (Brazil) and lockdown in Spain associated with protective measures on the epidemic of CoViD-19.

Coronavirus disease 2019 (CoViD-19), with the fatality rate in elder (60 years old or more) being much higher than young (60 years old or less) patients, was declared a pandemic by the World Health Organization on March 11, 2020. A mathematical model considering young and elder subpopulations under different fatality rates was formulated based on the natural history of CoViD-19 to study the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The model considered susceptible, exposed, asymptomatic, pre-symptomatic, mild CoViD-19, severe CoViD-19, and recovered compartments, besides compartments of isolated individuals and those who were caught by test. This model was applied to study the epidemiological scenario resulting from the adoption of quarantine (isolation or lockdown) in many countries to control the rapid propagation of CoViD-19. We chose as examples the isolation adopted in São Paulo State (Brazil) in the early phase but not at the beginning of the epidemic, and the lockdown implemented in Spain when the number of severe CoViD-19 cases was increasing rapidly. Based on the data collected from São Paulo State and Spain, the model parameters were evaluated, and we obtained a higher estimation for the basic reproduction number R0 (9.24 for São Paulo State, and 8 for Spain) compared to the currently accepted estimation of R0 around 2 using the SEIR (susceptible, exposed, infectious, and recovered compartments) model. In comparison with the lockdown in Spain, the relatively early adoption of the isolation in São Paulo State resulted in enlarging the period of the first wave of the epidemic and delaying its peak. The model allowed to explain the flattening of the epidemic curves by quarantine when associated with the protective measures (face mask, washing hands with alcohol and gel, and social distancing) adopted by the population. The description of the epidemic under quarantine and protections can be a background to foreseen the epidemiological scenarios from the release strategies, which can help guide public health policies by decision-makers.

Atualizando e expandindo o universo de: "Uma nova classe de doenças ­ doenças autoinflamatórias" / Updating and expanding the universe of: "A new class of diseases ­ autoinflammatory disorders"

As síndromes autoinflamatórias são doenças raras, genéticas de envolvimento prioritário da imunidade inata. Avanços nas técnicas de sequenciamento genético permitiram dissecar os genes envolvidos nestas doenças, continuamente organizando o quebra-cabeça genético e fisiopatológico de tais desordens. Este artigo revisa os últimos achados genéticos com seus respectivos fenótipos, código OMIM e ORPHA. Além disso, sugere cautela na triagem clínica e na indicação de métodos restritivos de sequenciamentos genéticos.

Autoinflammatory diseases comprise a group of rare, genetic disorders with priority involvement of innate immunity. Advances in genetic sequencing techniques allowed genetic dissection of genes involved in these diseases, with continuous organization of the genetic and pathophysiologic puzzle of these disorders. This article reviews the most recent genetic findings linked to respective phenotypes and OMIM and ORPHA codes. Moreover, it suggests caution in clinical screening and genetic sequencing indication with restrictive genetic panels.

Síndrome de Hiper IgD: espectros clínicos, achados genéticos e condutas terapêuticas / Hyper-IgD syndrome: clinical spectrum, genetic findings, and therapeutic approaches

A deficiência de mevalonato quinase (MVK; MIM #142680; ORPHA #343) é uma doença genética, espectral, rara, associadas a mutações ao longo do gene MVK causando distúrbios na síntese do colesterol, que culminam em: inflamação sistêmica com febre, adenopatia, sintomas abdominais e outros achados clínicos. Enquanto no polo leve da doença os achados mais comuns são febres recorrentes com linfadenopatia, no polo mais grave adiciona-se o acometimento do sistema nervoso central (meningites assépticas, vasculites e atraso do desenvolvimento neuropsicomotor) e do sistema hematopoiético (síndrome de ativação macrofágica). Apesar de inúmeras terapêuticas, os bloqueadores da interleucina-1 ainda são os únicos medicamentos capazes de controlar a doença e de impedir a evolução para amiloidose. Os estudos atuais visam tentar novos tratamentos, como o transplante de células-tronco hematopoiéticas, ou mesmo a terapia gênica.

Mevalonate kinase deficiency (MVK; MIM #142680; ORPHA #343) is a rare spectral genetic disorder linked to mutations along the MVK gene leading to impaired cholesterol synthesis, clinically observed as systemic inflammation with fever, adenopathy, abdominal manifestations, and other clinical findings. While on mild forms recurrent fever with lymphadenopathy is commonly observed, severe forms add to that neurological (aseptic meningitis, vasculitis, and neuropsychomotor developmental delay) and hematopoietic involvement (macrophage activation syndrome). Despite of several therapeutic approaches, blocking interleukin-1 is the only effective method to control the disease and prevent the development of systemic amyloidosis. Ongoing studies aim to test new treatments, such as hematopoietic stem cell transplantation and gene therapy.

Hiperplasia gengival durante uso de ciclosporina / Gingival hyperplasia during cyclosporine use

Paciente do sexo masculino, com 24 anos, portador de dermatite atópica desde o primeiro ano de vida. Começou a evoluir com forma grave da dermatite atópica aos 17 anos, e devido à refratariedade clínica ao tratamento convencional tópico, foi encaminhado para serviço de referência. Após otimizar os cuidados com uso de emolientes, corticoides tópicos e cursos de antibioticoterapia, manteve persistência de eczema generalizado, com SCORAD oscilando entre 40 e 50 no período de 4 meses. Dessa forma, optou-se por terapia sistêmica, sendo iniciado o uso de ciclosporina oral na dose de 200 mg. A resposta terapêutica com a ciclosporina foi percebida após 4 semanas, sendo refletida na redução do escore de gravidade (SCORAD=10). Durante o seguimento, além da melhora clínica, eram monitorados potenciais eventos adversos. O paciente fez uso da ciclosporina durante 5 anos sem apresentar eventos adversos, com necessidade de aumento de dose para 300 mg/dia dois anos após início da medicação. Porém, neste quinto ano de uso da ciclosporina, o paciente apresentou hipertrofia gengival importante. Assim, optou-se por reduzir a dose de ciclosporina de 300 para 200 mg/dia. Nenhum outro sinal ou sintoma foi observado, e os exames laboratoriais também não mostraram qualquer toxicidade. O paciente se mostrou resistente à redução da medicação, pois o temor de piora das lesões de pele o aflige muito. Orientamos sobre a necessidade de melhorar a higiene bucal de forma disciplinada, e agendamos reavaliação clínica mensal. Além disso, foi encaminhado para avaliação odontológica.

A 24-year-old man had atopic dermatitis since the first year of life. He first developed a severe form of atopic dermatitis at the age of 17, and because of clinical refractoriness to conventional topical treatment, he was referred to an excellence center. After care was optimized with emollients, topical corticosteroids and courses of antibiotic therapy, generalized eczema persisted, with Scoring Atopic Dermatitis (SCORAD) score oscillating between 40 and 50 in a period of 4 months. Thus, systemic therapy was chosen, with use of oral cyclosporine at a dose of 200 mg. Therapeutic response with cyclosporine was observed after 4 weeks, with a reduction in the severity score (SCORAD = 10). During followup, in addition to clinical improvement, potential adverse events were monitored. The patient used cyclosporine for 5 years with no adverse events, requiring a dose increase to 300 mg 2 years after initiating the medication. However, in the 5th year of cyclosporine use, the patient had significant gingival hyperplasia. Thus, we decided to reduce the dose of cyclosporine from 300 to 200 mg. No other signs or symptoms were observed and laboratory tests also showed no toxicity. The patient was resistant to reducing the medication, as he feared the skin lesions would aggravate. We advised him on the need to improve oral hygiene in a disciplined manner and scheduled a monthly clinical reevaluation. In addition, he was referred to dental evaluation.

A case report of a novel compound heterozygous mutation in a Brazilian patient with deficiency of Interleukin-1 receptor antagonist (DIRA).

BACKGROUND: Deficiency of the natural antagonist of interleukin-1 was first described in 2009 and so far 20 patients has been reported. In Brazil just two cases have been reported both carrying the same homozygous 15 bp deletion. Blocking interleukin-1 has changed rate survival for DIRA patients. The use of anakinra and rilonacept has been reported safe and efficient, whereas the selective blockade of interleukin-1 beta, using the monoclonal antibody canakinumab has been reported in a single case only. CASE PRESENTATION: Here we report a case of a 7 years old Brazilian boy that presented with recurrent episodes of systemic inflammation with severe disabling osteomyelitis with mild pustular skin rash. A Next Generation Sequencing gene panel allowed to detect two pathogenic mutations in the IL1RN gene, described in compound heterozygosity. Corticosteroids was effective in controlling inflammation and anti-IL1 beta blocker triggered disease flare. Complete clinical control could be achieved using IL-1 receptor antagonist. CONCLUSIONS: DIRA is a severe, life threatening autoinflammatory condition with low numbers of patients described all over the world. The mutation p.Asp72_Ile76del in IL1RN is presented in all Brazilian DIRA patients already described and p.Q45* (rs1019766125) is a new mutation affecting the IL1RN gene. Following the pathogenesis of DIRA, blocking both subunits of interleukin one as well as antagonizing the receptor using anakinra or rilonacept seems to be effective. There is just one report using canakinumab for the treatment of DIRA and this is the first report of disease flare using this drug.

Hemorragia digestiva alta como complicação de esofagite eosinofílica / Upper gastrointestinal bleeding as a complication of eosinophilic esophagitis

A hemorragia digestiva alta (HDA) é uma condição médica comum, que permanece com uma taxa de mortalidade aproximadamente de 10%. Doenças alérgicas habitualmente não configuram risco para HDA. Entretanto, o aumento recente de doenças alérgicas que afetam cronicamente o trato digestório poderia mudar esse cenário. Este artigo relata um caso de HDA após hematêmese provocada por impactação alimentar. Realizada endoscopia digestiva alta (EDA) e diagnosticada esofagite eosinofílica (EoE), que após tratamento adequado, apresentou melhora dos sintomas. A EoE é uma doença inflamatória crônica esofágica emergente, com aumento do número de casos diagnosticados ao redor do mundo. Atualmente, considera-se a causa mais prevalente de disfagia e impactação alimentar em crianças e adultos jovens. Os sintomas de EoE não são específicos para cada faixa etária, e podem variar desde sintomas mais leves, como sintomas de doença do refluxo gastroesofágico, até disfagia e impactação alimentar. Existe atraso no diagnóstico e tratamento, propiciando um aumento de complicações, cujo risco mais temido seria rotura do esôfago. Revisando a literatura até o presente relato, constatamos que a EoE nunca foi descrita como uma causa de HDA. Além da apresentação incomum da HDA levando ao diagnóstico de EoE, esse caso ressalta a importância do atendimento multidisciplinar e cooperação entre especialidades. Portanto, há necessidade de diagnóstico mais precoce e preciso, buscando ampliar o conhecimento para não negligenciar características específicas da disfagia, e evitar complicações com o tratamento adequado.

Upper gastrointestinal bleeding (UGIB) is a common medical condition whose mortality rate remains at about 10%. Allergic diseases are no usual risk for UGIB. However, the recent increase in allergic diseases that chronically affect the gastrointestinal tract could change this scenario. This article reports a case of UGIB after hematemesis caused by food impaction. Upper gastrointestinal endoscopy was performed and eosinophilic esophagitis (EoE) was diagnosed. EoE is an emerging chronic esophageal inflammatory disease with an increasing number of diagnosed cases around the world. Currently, it is considered the most prevalent cause of dysphagia and food impaction in children and young adults. EoE symptoms are not specific to each age group and may range from mild symptoms such as those of gastroesophageal reflux disease to dysphagia and food impaction. There is a delay in diagnosis and treatment that leads to increased complications, including esophageal rupture, the most feared risk. Our literature review showed that EoE had never been described as a cause of UGIB. In addition to the unusual presentation of UGIB leading to the diagnosis of EoE, this case highlights the importance of multidisciplinary care and cooperation between specialties. Therefore, there is a need for earlier and more accurate diagnosis, which would lead to expanded knowledge that could be used to not disregard specific characteristics of dysphagia and avoid complications with appropriate treatment.

Immunophenotypical Characterization of a Brazilian POIS (Post-Orgasmic Illness Syndrome) Patient: Adding More Pieces to Puzzle.

Post-orgasmic illness syndrome (POIS) is a rare condition characterized by post-ejaculatory symptoms. Here is reported the first Brazilian POIS patient. Immunological investigation did not confirm the previous hypothesis of a hypersensitivity reaction. Cell immunophenotyping comparing healthy individuals produced evidence of abnormalities not associated to clinical manifestations. The patient was submitted to specific immunotherapy with transient clinical response and was referred to a psychologist but did not demonstrate clinical improvement of symptoms. Therefore, etiology of POIS remains unclear.

Mepolizumabe na doença respiratória exacerbada por aspirina - DREA / Mepolizumab in aspirin-exacerbated respiratory disease - AERD

Relato de caso que ilustra a eficácia e a segurança do uso do mepolizumabe na doença respiratória exacerbada por aspirina (DREA). A utilização de anticorpo monoclonal no tratamento desta doença respiratória de difícil tratamento tem possibilitado o controle da inflamação crônica e o maior conhecimento sobre a fisiopatogenia da doença.

This case report shows the efficacy and safety of mepolizumab in aspirin-exacerbated respiratory disease (AERD). The use of monoclonal antibodies in the treatment of this severe disease has provided improved control of chronic inflammation and greater understanding about the pathophysiology of the disease.

Síndrome PFAPA (febre periódica, aftas orais, faringite e adenite cervical) em crianças e adultos / PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenitis) syndrome in children and adults

A síndrome PFAPA (febre periódica, aftas orais, faringite e adenite cervical) é a forma mais comum das doenças autoinflamatórias. Trata-se de uma doença rara, não genética, bimodal, usualmente com início dos sintomas antes dos 5 anos de vida, que também pode prolongar-se ou iniciar-se na vida adulta. A prevalência é variável em todo o mundo, e não há dados estatísticos da doença no Brasil. Diversos pontos da doença são discutíveis, como os critérios diagnósticos, as avaliações laboratoriais, a ausência de mutações genéticas específicas e a abordagem terapêutica e prognóstica. Este trabalho tem como objetivo rever, de forma narrativa e crítica, aspectos relacionados ao diagnóstico e tratamento da síndrome PFAPA em adultos e crianças. Foram feitas buscas nas redes de dados PubMed, Bireme e Cochrane, utilizando o acrônimo PFAPA sem auxílio de qualquer filtro. Quanto ao diagnóstico, os critérios pediátricos foram adaptados para os adultos, com análises variadas e divergentes. Há a necessidade pujante de desenvolver um consenso com diretrizes de diagnóstico de pacientes em populações bem caracterizadas para melhor diagnosticar a doença. Já em relação ao tratamento, a cirurgia com remoção das tonsilas é considerada curativa, com necessidade de se manter acompanhamento após o procedimento para confirmação da remissão da doença. As drogas poupadoras de corticoide ainda são incertas, e o uso de imunobiológicos deve ser reservado somente para pacientes refratários ao tratamento cirúrgico e com grande impacto na qualidade de vida.

PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenitis) syndrome is the most common form of autoinflammatory disease. It is a rare, non-genetic, bi-modal disease, usually with onset of symptoms before the age of 5 years, which may also be prolonged or start in adult life. The prevalence varies worldwide and there are no specific statistical data in Brazil. Several aspects of the disease are debatable, such as diagnostic criteria, laboratory evaluations, absence of specific genetic mutations, and therapeutic and prognostic approach. This paper aims to review in a narrative and critical manner aspects related to diagnosis and treatment of PFAPA syndrome in adults and children. PubMed, Bireme and Cochrane databases were searched using the acronym PFAPA without any filter. Regarding diagnosis, pediatric criteria were adapted for use in adults, with varied and divergent analyses. There is a strong need to develop consensus diagnostic guidelines for patients in well-characterized populations to better diagnose the disease. Regarding treatment, tonsillectomy is considered curative, requiring follow-up after the procedure to confirm remission of the disease. Corticosteroid-sparing agents remain uncertain, and the use of immunobiological agents should be reserved only for patients who are refractory to surgical treatment and experience a great impact on quality of life.

Sensitization to cat allergen and its association with respiratory allergies: cross-sectional study.

Cats are a significant source of allergens that contribute towards worsening of allergic diseases. The aim of this study was to investigate the association between sensitization to cat allergens and allergic respiratory diseases.This was an observational retrospective study based on the skin pricktests results of patients at a tertiary-level hospital in São Paulo. A total of 1,985 test results were assessed. The prevalence of sensitization to cat allergen was 20% (399 patients). Our data indicated that in this population of atopic patients, a positive skin prick test result for cat allergen was not associated significantly with a diagnosis of respiratory allergy.

Sensitization to cat allergen and its association with respiratory allergies: cross-sectional study

ABSTRACT Cats are a significant source of allergens that contribute towards worsening of allergic diseases. The aim of this study was to investigate the association between sensitization to cat allergens and allergic respiratory diseases.This was an observational retrospective study based on the skin pricktests results of patients at a tertiary-level hospital in São Paulo. A total of 1,985 test results were assessed. The prevalence of sensitization to cat allergen was 20% (399 patients). Our data indicated that in this population of atopic patients, a positive skin prick test result for cat allergen was not associated significantly with a diagnosis of respiratory allergy.

Production of the first effective hyperimmune equine serum antivenom against Africanized bees.

Victims of massive bee attacks become extremely ill, presenting symptoms ranging from dizziness and headache to acute renal failure and multiple organ failure that can lead to death. Previous attempts to develop specific antivenom to treat these victims have been unsuccessful. We herein report a F(ab)(´)(2)-based antivenom raised in horse as a potential new treatment for victims of multiple bee stings. The final product contains high specific IgG titers and is effective in neutralizing toxic effects, such as hemolysis, cytotoxicity and myotoxicity. The assessment of neutralization was revised and hemolysis, the primary toxic effect of these stings, was fully neutralized in vivo for the first time.

Novel allergens from ancient foods: Man e 5 from manioc (Manihot esculenta Crantz) cross reacts with Hev b 5 from latex.

SCOPE: Manioc (Manihot esculenta) is a tuber mainly consumed in the Southern Hemisphere and used worldwide by food and chemistry industry. We aimed to recombinantly produce and characterize the first manioc allergen and evaluate its IgE reactivity in sera of Brazilian and Italian patients. METHODS AND RESULTS: The molecule, termed Man e5, was expressed in E. coli, characterized by amino acid analysis, mass spectrometry, circular dichroism, HPLC, and dynamic light scattering. A tertiary structural model of the protein was produced using bioinformatics and susceptibility to pepsin digestion was analyzed in vitro. Based on its high content of charged residues, heat stability, flexibility and lack of secondary structure elements, the allergen was determined a member of the intrinsically disordered protein family. Brazilian patients were selected based on manioc allergy and Italians based on latex allergy and sensitization to Hev b 5.71% of Brazilians and 40% of Italians were in vitro IgE positive to Man e5. Cross-inhibition assays suggest a possible involvement of this allergen in the latex-fruit syndrome. CONCLUSION: Man e5, the first purified allergen from manioc demonstrates IgE cross-reactivity with Hev b 5. Data suggest Hev b 5 might act as primary sensitizer and could therefore lead to allergic manifestations upon manioc consumption without prior exposition.

Determinação de IgE específica in vivo e in vitro após a imunoterapia específica com veneno de himenópteros: é parâmetro para avaliação do sucesso do tratamento? / In vivo and in vitro specific IgE determination after specific immunotherapy with Hymenoptera venom: parameter to evaluate treatment success?

OBJETIVO: Comparar os níveis séricos de anticorpos IgE veneno-específicos e a reatividade em testes cutâneos antes e após 3 anos de imunoterapia específica com veneno de himenópteros. MÉTODO: Pacientes foram selecionados para imunoterapia de acordo com a história clínica e pesquisa de anticorpos IgE veneno-específicos (ImmunoCap, Phadia, Brasil) e testes cutâneos (prick test e intradérmico). Após 3 anos de imunoterapia, os pacientes foram avaliados sobre ferroadas acidentais e foram repetidos a IgE sérica e o teste cutâneo. RESULTADOS: Trinta e cinco pacientes foram avaliados. Dos que fizeram imunoterapia com veneno de abelha, 56% tiveram diminuição dos níveis de IgE por ImmunoCap, 71% permaneceram com teste cutâneo positivo, e 5% apresentaram sensibilização ao veneno de vespa, que não havia sido detectada na avaliação inicial. Para os que fizeram imunoterapia com veneno de vespa, 80% tiveram diminuição no nível de IgE sérica, 88% apresentaram teste cutâneo negativo, e 5% apresentaram sensibilização ao veneno de abelha. Dos que fizeram imunoterapia com veneno de formiga, 92% tiveram diminuição dos níveis de IgE sérica específica, 78% permaneceram com teste cutâneo positivo, e 10%, apresentaram sensibilização para abelha e vespa. Não houve reação sistêmica dos pacientes que apresentaram ferroadas acidentais (86% dos pacientes alérgicos a abelha, 75% a vespa e 82% a formiga). CONCLUSÃO: A imunoterapia por pelo menos 3 anos foi efetiva, pois todos os pacientes que foram ferroados acidentalmente não apresentaram reações sistêmicas. Nossos resultados também demonstraram que tanto a IgE sérica específica assim como os testes cutâneos não servem como parâmetros de sucesso no tratamento, pois a maioria permanece com positividade, no entanto sem reatividade clínica.

Objective: To compare serum levels of venom-specific IgE antibodies and skin test reactivity before and after 3 years of specific immunotherapy with Hymenoptera venom. Method: Patients were selected for immunotherapy according to clinical history, presence of venom-specific IgE (ImmunoCAP, Phadia, Brazil), and positive skin tests (prick test and intradermal test). After 3 years of immunotherapy, patients were inquired about accidental stings, and both serum IgE and skin tests were repeated. Results: Thirty-five patients were evaluated. Among those who had received bee venom immunotherapy, 56% showed lower levels of specific IgE on ImmunoCAP, 71% had positive skin tests, and 5% showed sensitization to wasp venom that was not detected at baseline. Of those who had received immunotherapy with wasp venom extract, 80% showed lower levels of serum IgE, 88% had negative skin tests, and 5% showed sensitization to bee venom. Finally, among patients treated with fire ant immunotherapy, 92% showed lower specific IgE levels; 78% had positive skin tests, and 10% presented sensitization to bee and wasp venoms. There were no systemic reactions in patients who had been accidentally stung (86% of patients allergic to bee, 75% to wasp, and 82% to fire ant). Conclusion: Immunotherapy for at least 3 years was effective, as none of the patients accidentally stung showed systemic reactions. Our results also showed that neither serum specific IgE nor skin tests are reliable parameters for the evaluation of treatment success, as the majority of patients remained positive, however without clinical reactivity.