Mastócitos e síndrome de ativação mastocitária: o que há de novo? / Mast cells and mast cell activation syndrome: what's new?

Os mastócitos são as principais células efetoras da resposta alérgica aguda, desempenhando também um papel importante na angiogênese, tolerância imunológica, regulação da fibrinólise, regeneração neuronal e osteoclastogênese. Localizam-se maioritariamente na pele e nas mucosas do intestino e pulmões, onde exercem uma função "sentinela". As síndromes de ativação mastocitária são caracterizadas pela ocorrência de episódios recorrentes de manifestações clínicas resultantes da libertação de mediadores mastocitários. Esta constitui-se como entidade complexa com um espectro de sintomas associados, representando um desafio diagnóstico e terapêutico. Nesta revisão, os autores pretendem apresentar uma visão geral sobre a estrutura e função dos mastócitos e sobre os critérios diagnósticos e abordagem terapêutica da síndrome de ativação mastocitária.

Mast cells are the main effector cells of acute allergic response, also playing an important role in angiogenesis, immune tolerance, regulation of fibrinolysis, neuronal regeneration, and osteoclastogenesis. They are generally located in the skin and mucous membranes of the intestines and lungs, where they perform a "sentinel" function. Mast cell activation syndrome is characterized by recurrent clinical manifestations resulting from the release of mast cell mediators. This complex entity, which involves a spectrum of associated symptoms, is a diagnostic and therapeutic challenge. In this article we overview of the structure and function of mast cells, in addition to the diagnostic criteria and therapeutic approaches to mast cell activation syndrome.

Brief Introduction of Mast Cell Activation Syndrome / 胃肠病学

Mast cell activation syndrome (MCAS) is a chronic multisystem disorder caused by inappropriate activation of mast cells. The gastrointestinal tract harbors a large population of mast cells and is easily to be involved by MCAS. Being an under-recognized disease, and because gastrointestinal symptoms are frequently reported, MCAS is often misdiagnosed as functional gastrointestinal disorders(FGIDs). Definite diagnosis should be based on the clinical manifestations, detection of mast cell mediators and pathological examination; and above all, other organic diseases should be excluded. Routine symptomatic treatment is often ineffective in relieving gastrointestinal symptoms. In addition to avoiding triggers, the best treatment modalities are mast cell mediator antagonists and regulation of the activation process of mast cells. In this article, the function of mast cells, and the clinical manifestations, diagnosis, differential diagnosis and treatment of MCAS were briefly introduced.

Uma visão atualizada da anafilaxia idiopática: a ausência de evidência não é a evidência de ausência / An updated view of idiopathic anaphylaxis: absence of evidence is not evidence of absence

A anafilaxia idiopática não apresenta etiologia conhecida. A sua prevalência é estimada entre 10-35% de todas as modalidades de anafilaxia. A sintomatologia apresentada é a mesma de qualquer outra anafilaxia: urticária, angioedema, ruborização, prurido, hipotensão arterial, taquicardia, manifestações gastrointestinais (disfagia, náusea, vômitos, cólicas abdominais, diarreia), asma, edema laríngeo, tontura e síncope. A mortalidade é rara. Não há transmissão genética, mas 40% dos pacientes são atópicos. É mais frequente nos adultos do que nas crianças, e principalmente em mulheres. É um diagnóstico de exclusão. Ocorre ativação mastocitária com desgranulação citoplasmática dos mediadores de anafilaxia (triptase, histamina, entre outros). É uma anafilaxia com boa resposta aos corticoides, e, portanto, caso não haja resposta adequada a doses eficazes de prednisona/prednisolona, o seu diagnóstico deve ser revisto. O diagnóstico diferencial da anafilaxia idiopática inclui: a mastocitose sistêmica indolente, síndromes de ativação mastocitária monoclonais, alergia à galactose-alfa-1,3 galactose, anafilaxia induzida por exercícios (com e sem dependência alimentar e medicamentosa), angioedema hereditário (congênito e adquirido), feocromocitoma, síndrome carcinoide, anafilaxia oral acarina, alergia ao Anisakis simplex, disfunção das cordas vocais, síndrome escombroide, alergia ao sêmen, alergia ao látex, manifestações psicossomáticas (síndrome do pânico, globus hystericus e a síndrome de Münchausen), bem como as tradicionais e mais frequentes modalidades de anafilaxia (alergia a alimentos, medicamentos e insetos). O tratamento na crise aguda da anafilaxia idiopática é o mesmo do que nas demais anafilaxias, incluindo a administração intramuscular imediata de epinefrina. Deve haver uma generosa e prolongada prescrição de corticoterapia oral, e também a instituição de medicação preventiva (anti-histamínicos anti- H1 e anti-H2, cetotifeno, albuterol oral, montelucaste, cromoglicato de sódio, e por último o omalizumabe). Os pacientes devem portar epinefrina autoinjetora e ser instruídos sobre como agir em caso de um episódio anafilático. Eles respondem bem à administração de epinefrina. A corticoterapia oral, por 4-6 semanas, pode induzir uma remissão completa.

Idiopathic anaphylaxis is a condition of unknown etiology. Its prevalence ranges from 10 to 35% of all cases of anaphylaxis. Clinical symptoms and signs are those of classic anaphylaxis, including urticaria, angioedema, flushing, itching, hypotension, tachycardia, gastrointestinal manifestations (dysphagia, nausea, vomiting, abdominal cramps, and diarrhea), asthma, laryngeal edema, dizziness, and syncope. Mortality is rare. There is no genetic transmission, but about 40% of patients are atopic. It is more common in adults than in children, affecting mainly women. It is considered a diagnosis of exclusion of other known forms of anaphylaxis. Mast cell activation occurs with cytoplasmatic degranulation of mediators of anaphylaxis (tryptase and histamine, among others). Because idiopathic anaphylaxis is a steroid-responsive condition, if it is not controlled with adequate doses of prednisone/prednisolone, the diagnosis should be challenged. The differential diagnosis of idiopathic anaphylaxis includes indolent systemic mastocytosis, clonal mast cell activation syndromes, galactose-alpha-1,3- galactose allergy, exercise-induced anaphylaxis (both food- and drug-dependent and -independent), hereditary angioedema (congenital and acquired), pheochromocytoma, carcinoid syndrome, oral mite anaphylaxis, Anisakis simplex allergy, vocal cord dysfunction, scombroid poisoning, semen allergy, latex allergy, psychosomatic conditions (panic attacks, globus hystericus, and Münchausen syndrome), and the classic forms of anaphylaxis (food, drug, and insect allergies). Treatment of acute idiopathic anaphylaxis is the same as in the other forms of anaphylaxis, including intramuscular epinephrine, but with prolonged oral corticosteroid therapy. It might also include other oral preventive medications (H1 and H2 antihistamines, ketotifen, oral albuterol, montelukast, sodium cromoglycate, and recently omalizumab). Patients should have an epinephrine auto-injector and be instructed on self-management of anaphylaxis. Good response to epinephrine is observed, and oral corticosteroid therapy for 4-6 weeks can induce complete remission.

Anti-Allergic ‘Benifuuki’ Green Tea / 日本補完代替医療学会誌

We have reported that <i>O</i>-methylated EGCG (epigallocatechin-3-<i>O</i>-(3-<i>O</i>-methyl)gallate (EGCG3″Me) had 2.5-fold anti-allergic action compared with EGCG (epigallocatechin gallate), and that the tea (<i>Camellia sinensis </i>L.) cultivar ‘Benifuuki’ was rich in EGCG3″Me. The EGCG3″Me content was high and caffeine content decreased in fully-matured tea leaves in second or third crop season, and EGCG3″Me was disappeared under black tea manufacturing process. ‘Benifuuki’ is a cultivar with strong resistance for diseases, strong vigor of plant, many yield and excellent fragrance. The EGCG3″Me strongly inhibited mast cell activation through the prevention of tyrosine phosphorylation (Lyn, Syk and Btk) of cellular protein, the phosphorylation of myosin light chain and the expression of Fcepsolon RI, and histamine/leukotrienes release. Furthermore, over one consecutive month intake of ‘Benifuuki’ green tea was useful for reduction of some symptoms derived from Japanese cedar pollinosis, and did not affect any normal immune response in the subjects with Japanese cedar-pollinosis. So, in cooperation with food companies, we developed PET beverage and sweet using ‘Benifuuki’ green tea.<br>

Inhibitory Effect of Polysaccharide Fraction from Cortex Mori on Compound 48/80-Induced Mast Cell Activation / 대한면역학회지

Cortex mori (Morus alba L.: Sangbaikpi), the root bark of mulberry tree, has been used as an antiphlogistic, diuretic, and expectorant in herbal medicine. Previous studies have demonstrated that the phenolic extract of Cortex mori have hypotensive, hypoglycemic, antifungal, antiviral, antiinflammatory, and anticancer effects, and the hot water extract from Cortex mori has inhibitory effects on compound 48/80- induced mast cell degranulation and histamine release from rat peritoneal mast cells (RPMCs). This study was perforrned to investigate the effects of polysaccharide fraction from Cortex mori (PFCM) on compound 48/80-induced degranulation, histamine release, calcium influx, changes of intracellular cAMP and cGMP level, and morphological changes of RPMCs. The results were summarized as follows. 1) Compound 48/80-induced cytomorphological changes such as swelling, degranulation, intracellular vacuoles, and interrupted cell boundary were significantly inhibited by pretreatment with either hot water or polysaccaride fractions frorn Cortex mori (PFCM), 2) the compound 48/80-induced histamine release from RPMCs pretreated with PFCM was significantly inhibited, compared to that of control without PFCM pretreatment, 3) the PFCM inhibited remarkably the compound 48/80-induced calcium influx into the RPMCs, 4) the PFCM increased significantly the intracellular cAMP levels and decreased the intracellular cGMP levels of RPMCs, compared to those of normal control, and 5) the compound 48/80-induced cAMP levels of RPMCs pretreated with PFCM were significantly increased, compared to those of positive control without PFCM, and the compound 48/80-induced cGMP levels of RPMCs pretreated with PFCM were remarkably decreased, compared to those of positive control without PFCM. From the above results, it is suggested that PFCM have an activity to inhibit the compound 48/80-induced mast cell activation.