背景:罕见的自身炎症性疾病(AIDs),包括Cryopyrin相关的周期性综合征(CAPS),肿瘤坏死受体相关的周期性综合征(TRAPS)和甲羟戊酸激酶缺乏症(MKD)/高IgD综合征(HIDS)在遗传上定义并表征为反复发热和炎症器官表现。早期诊断和早期开始有效治疗控制炎症并防止器官损伤。德国小儿风湿病学会(GKJR)的PRO-KIND倡议旨在在全国范围内协调风湿性疾病患儿的诊断和管理。亲王CAPS/TRAPS/MKD/HIDS工作组的任务是开发基于证据的,共识诊断和管理方案,包括第一个AID治疗目标策略。
方法:成立了国家CAPS/TRAPS/MKD/HIDS专家工作组,定义了其目标,并进行了全面的文献综述,综合了最近(2013年至2018年)发表的证据,包括所有可用的诊断和管理建议.一般和特定疾病的陈述以2015年SHARE建议为基础。讨论了一个迭代的专家评审过程,调整和完善这些声明。最终,GKJR成员审查了拟议的共识声明,80%的协议是强制性的。批准的陈述被整合到三个疾病特异性共识治疗计划(CTP)中。这些都是为了能够实施以证据为基础的,标准化护理融入临床实践。
结果:由12名德国和奥地利儿科风湿病学家组成的CAPS/TRAPS/MKD/HIDS专家工作组完成了证据综合,并根据SHARE建议框架修改了总共38项声明。在迭代审查中,36在最终的GKJR成员调查中达到了80%的强制性协议门槛。其中包括9项总体原则和27项针对疾病的声明(CAPS为7项,11陷阱,9MKD/HIDS)。基于综合证据建立了诊断算法。陈述被整合到CAPS的诊断和疾病活动特异性治疗目标CTP中,陷阱和MKD/HIDS。
结论:亲王CAPS/TRAPS/MKD/HIDS工作组建立了第一个基于证据的,三种罕见的遗传性自身炎症性疾病的可操作的治疗到目标的共识治疗计划。这些提供了快速评估的途径,有效控制疾病活动和调整治疗。它们的实施将减少护理的变化,并优化AID儿童的健康结果。
BACKGROUND: Rare autoinflammatory diseases (AIDs) including Cryopyrin-Associated Periodic Syndrome (CAPS), Tumor Necrosis Receptor-Associated Periodic Syndrome (TRAPS) and Mevalonate Kinase Deficiency Syndrome (MKD)/ Hyper-IgD Syndrome (HIDS) are genetically defined and characterized by recurrent fever episodes and inflammatory organ manifestations. Early diagnosis and early start of effective therapies control the inflammation and prevent organ damage. The PRO-KIND initiative of the German Society of Pediatric Rheumatology (GKJR) aims to harmonize the diagnosis and management of children with rheumatic diseases nationally. The task of the PRO-KIND CAPS/TRAPS/MKD/HIDS working group was to develop evidence-based,
consensus diagnosis and management protocols including the first AID treat-to-target strategies.
METHODS: The national CAPS/TRAPS/MKD/HIDS expert working group was established, defined its aims and conducted a comprehensive literature review synthesising the recent (2013 to 2018) published evidence including all available recommendations for diagnosis and management. General and disease-specific statements were anchored in the 2015 SHARE recommendations. An iterative expert review process discussed, adapted and refined these statements. Ultimately the GKJR membership vetted the proposed
consensus statements, agreement of 80% was mandatory for inclusion. The approved statements were integrated into three disease specific
consensus treatment plans (CTPs). These were developed to enable the implementation of evidence-based, standardized care into clinical practice.
RESULTS: The CAPS/TRAPS/MKD/HIDS expert working group of 12 German and Austrian paediatric rheumatologists completed the evidence synthesis and modified a total of 38 statements based on the SHARE recommendation framework. In iterative reviews 36 reached the mandatory agreement threshold of 80% in the final GKJR member survey. These included 9 overarching principles and 27 disease-specific statements (7 for CAPS, 11 TRAPS, 9 MKD/HIDS). A diagnostic algorithm was established based on the synthesized evidence. Statements were integrated into diagnosis- and disease activity specific treat-to-target CTPs for CAPS, TRAPS and MKD/HIDS.
CONCLUSIONS: The PRO-KIND CAPS/TRAPS/MKD/HIDS working group established the first evidence-based, actionable treat-to-target
consensus treatment plans for three rare hereditary autoinflammatory diseases. These provide a path to a rapid evaluation, effective control of disease activity and tailored adjustment of therapies. Their implementation will decrease variation in care and optimize health outcomes for children with AID.