mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-MCA-2662mimmun-2662Research ArticleОБЗОРЫREVIEWSСиндром активации тучных клеток: новое мировоззрениеMast cell activation syndrome: A new outlookhttps://orcid.org/0000-0002-3196-8300МикрюковаН. В.MikryukovaN. V.

Микрюкова Наталья Васильевна – заведующая отделением профилактики и экспертизы профессиональной пригодности поликлиники.

197345, Санкт-Петербург, ул. Оптиков, 54

Тел.: 8 (812) 702-63-45 (доб. 3331)

Natalya V. Mikryukova - Head, Outpatient Department of Prevention and Expertise of Professional Suitability, A. Nikiforov Russian Center of Emergency and Radiation Medicine.

54 Optikov St St. Petersburg 197345

Phone: +7 (812) 702-63-45 (acc. 3331)

natalya@mikryukov.infoКалининаН. М.KalininaN. M.

Доктор медицинских наук, профессор, главный научный сотрудник отдела лабораторной диагностики ФГБУ «ВЦЭРМ им. А.М. Никифорова» МЧС России; профессор кафедры иммунологии ФГБОУ ВО «ПСПбГМУ им. ак. И.П. Павлова».

Санкт-Петербург

PhD, MD (Medicine), Professor, Chief Research Associate, Department of Laboratory Diagnostics, A. Nikiforov Russian Center of Emergency and Radiation Medicine; Professor, Department of Immunology, First St. Petersburg State I. Pavlov Medical University.

St. Petersburg

doctkalin@mail.ruФГБУ «Всероссийский центр экстренной и радиационной медицины имени А.М. Никифорова» МЧС РоссииРоссияA. Nikiforov Russian Center of Emergency and Radiation MedicineRussian FederationФГБУ «Всероссийский центр экстренной и радиационной медицины имени А.М. Никифорова» МЧС России; ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова»РоссияA. Nikiforov Russian Center of Emergency and Radiation Medicine; First St. Petersburg State I. Pavlov Medical UniversityRussian Federation20231306202325612891298Copyright © Микрюкова Н.В., Калинина Н.М., 20232023Микрюкова Н.В., Калинина Н.М.Mikryukova N.V., Kalinina N.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2662

Синдром активации тучных клеток (САТК) является тяжелым рецидивирующим заболеванием, требующим стационарного лечения, в клинической картине которого присутствуют признаки анафилаксии. В статье представлены диагностические критерии, позволяющие дифференцировать САТК от других тяжелых, имеющих сходную симптоматику состояний, а также обсуждены локальные формы активации тучных клеток.

Консенсусной группой установлены четкие критерии для диагностики САТК. Эти согласованные критерии включают эпизодическое (рецидивирующее) появление типичных системных симптомов, которые вызываются медиаторами тучных клеток и затрагивают как минимум 2 системы органов; увеличение уровня триптазы в сыворотке крови, по крайней мере на 20% по сравнению с индивидуальным исходным уровнем триптазы плюс 2 нг/мл триптазы в течение 3-4 часов после реакции; положительный ответ на препараты, которые либо нацелены на медиаторы тучных клеток, либо на их эффекты.

Классификация САТК носит этиологический характер и подразделяется на первичный (клональный) САТК, вторичный САТК и идиопатический САТК. Первичный САТК определяется клональной экспансией тучных клеток и является системным мастоцитозом. При вторичном САТК нормальные тучные клетки активируются известными триггерами, например IgE. Если ни клональная экспансия, ни триггер активации тучных клеток не могут быть идентифицированы, состояние определяется как идиопатический САТК.

Особый интерес к САТК привлекла новая коронавирусная инфекция COVID-19, было высказано предположение, что тяжелый вариант течения COVID-19 обусловлен скрытым САТК, однако критерии САТК у этих пациентов не воспроизводились. При наличии локальных симптомов, например крапивницы, либо при поражении 1 органа, например изолированные желудочно-кишечные симптомы, и подозрении на активацию тучных клеток в основе патогенеза был введен термин «расстройство активации тучных клеток». Также в статье обсуждены несколько различных медиаторов, которые предлагаются для использования в диагностике САТК.

Однако гипердиагностика САТК влечет за собой риск пропустить основную патологию, не связанную с САТК, и требует дифференциальной диагностики с рядом заболеваний. При отсутствии тяжелых приступов (с гипотонией и шоком) вероятность САТК в целом очень низкая. Безусловно, пациенты с мастоцитозом и/или подтвержденной IgE-зависимой аллергией имеют более высокий риск развития САТК, но ключевым диагностическим маркером является связанное с событием повышение триптазы ТК по сравнению с исходным уровнем, измеренное в бессимптомном интервале. Когда повышение уровня триптазы достигает определенного порога (20% от исходного уровня плюс 2 нг/мл), весьма вероятен диагноз «САТК».

Mast Cell Activation Syndrome (MCAS) is a severe relapsing disease requiring inpatient treatment, with clinical pattern including the features of anaphylaxis. The article presents diagnostic criteria aimed for differentiation of MCAS from similar severe conditions as well as discusses local forms of mast cell activation. The consensus group has established distinct criteria for diagnosing MCAS. The agreed criteria include episodic (recurrent) occurrence of typical systemic symptoms caused by release of mast cell mediators and involve, at least, two organs; an increase in serum tryptase level by, at least, 20% over individual baseline tryptase plus  2 ng/mL tryptase during 3-4 hours of the pathological reaction; a positive response to drugs that either target mast cells mediators, or their effects. In principle, the classification of MCAS is based on its etiology being subdivided into primary (clonal) MCAS, secondary MCAS, and idiopathic MCAS. The primary MCAS is determined by clonal expansion of mast cells and is considered systemic mastocytosis. In secondary MCAS, normal mast cells are activated by the known triggers, e.g., IgE. If neither clonal expansion nor a trigger for mast cells activation are identified, the condition is defined as idiopathic MCAS.

The new COVID-19 infection has attracted particular interest in MCAS, since the severe course of COVID-19 was thought to develop due to latent MCAS, but the criteria for MCAS in these patients were not reproduced. In the presence of local symptoms, such as urticaria, or in cases of single-organ involvement, e.g., isolated gastrointestinal symptoms, and suspected mast cell activation being basic to pathogenesis, the term mast cell activation disorder was introduced. Moreover, the article discusses several different mediators that are proposed as markers in the diagnosis of MCAS.

However, over-diagnosis of MCAS entails the risk of missing the underlying pathology, which is not associated with MCAS, and requires differential diagnosis with a number of diseases. In the absence of severe attacks (with hypotension and shock), the likelihood of MCAS is generally very low. Of course, the patients with mastocytosis and/or confirmed IgE-dependent allergy are at higher risk of developing MCAS, but a   key diagnostic marker is an event-related increase in mast cells tryptase from baseline determined over the asymptomatic period. The diagnosis of MCAS is highly likely if the tryptase level rises above a certain threshold (20% of baseline plus 2 ng/mL).

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The authors declare that there are no conflicts of interest present.