Научно-практический журнал Международной организации Consensus in Pediatrics Лечение васкулитов, ассоциированных с антинейтрофильными цитоплазматическими антителами

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Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2016; 15: 5-13

Научно-практический журнал Международной организации Consensus in Pediatrics Лечение васкулитов, ассоциированных с антинейтрофильными цитоплазматическими антителами

Румянцев Александр Григорьевич

https://doi.org/10.24287/1726-1708-2016-15-2-5-13

Аннотация

Васкулиты, ассоциированные с антинейтрофильными цитоплазматическими антителами (АНЦА) (далее ААВ), включают гранулематоз с полиангиитом (ранее болезнь Вегенера, теперь ГП), микроскопический полиангиит (МП), эозинофильный гранулематоз с полиангиитом (ЭГП, ранее - синдром Чердж-Стросса) и заболевания отдельных органов, такие как почечный васкулит. Хотя и редко, ААВ возникает у детей и сопровождается тяжелыми проявлениями и смертностью, особенно на поздней стадии выявления заболевания. ААВ в большинстве случаев связаны с серологически определяемыми АНЦА. Антитела (АНЦА), направленные против протеиназы-3 (PR3) или миелопероксидазы (МПО) нейтрофильных лейкоцитов, в более чем 80% случаев связаны с ГП или МП. И наоборот, только 50% пациентов с ЭГП являются АНЦА-положительными; и если АНЦА присутствует, то в 75% случаев они направлены против МПО. Применение режимов индукции ремиссии циклофосфамидом (Цф) и высокими дозами кортикостероидов (КС) в течение последних 25 лет перевели ААВ из разряда смертельных в разряд хронически рецидивирующих заболеваний. Исследования по снижению токсичности Цф привели к использованию в поддерживающей терапии более безопасных иммуносупрессантов, таких как метотрексат (МТ) или азатиоприн (АЗА). В дальнейшем стратификация ААВ по степени тяжести выделила пациентов с легким и среднетяжелым течением заболевания, которых лечат с помощью протоколов, не включающих ЦФ. С 2011 г. в первой линии терапии ААВ был введен ритуксимаб, препарат могоклонального анти-СД-20 антитела. В статье обсуждается современная тактика лечения АНЦА-васкулитов у взрослых и детей.

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Pediatric Hematology/Oncology and Immunopathology. 2016; 15: 5-13

Scientific and Practical Journal Global Initiative for Consensus in Pediatrics Management of vasculites associated with anti-neutrophil cytoplasmic antibodies

Rumyanstev Alexandr G.

https://doi.org/10.24287/1726-1708-2016-15-2-5-13

Abstract

Vasculites associated with anti-neutrophil cytoplasmic antibodies (ANCA) (further AAV) include granulomatosis with polyangiitis (previously Wegener disease, now GPA ), microscopic polyangiitis (MP), eosinophilic granulomatosis with polyangiitis (EGPA, previously Churg-Strauss syndrome) and diseases of particular organs, such as renal vasculitis. Though rarely, AAV occurs in children and is accompanied by severe manifestations and mortality, especially in late diagnosis of disease. In most cases, AAV are associated with serologically detected ANCA. Antibodies (ANCA) directed against proteinase-3 (PR3) or myeloperoxidase (MPO) of neutrophils are associated with GPA or MP in more than 80% of cases. And vice versa, only 50% of patients with EGPA are ANCA-positive; and if ANCA are present, in 75% of cases they are directed against MPO. The use of regimens with cyclophosphamide (CP) and high doses of corticosteroids (CS) for remission induction in the past 25 years have transferred AAV from the category of lethal to chronically recurrent diseases. Research in reduction of cyclophosphamide toxicity have resulted in development of safer immunosuppressants for supportive therapy, such as methotrexate (MT) or azathioprine (AZA). Later, stratification of AAV by severity has singled out patients with mild and moderate courses of disease, who are treated according to protocols that do not include CP. Since 2011, rituximab, a monoclonal anti-CD-20 antibody, has been introduced as the first-line AAV therapy. The article discusses current tactics of management of ANCA-vasculites in adults and children.

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