目的:甲羟戊酸激酶缺乏症(MKD)是一种常染色体隐性自身炎性疾病,其特征是反复发生的全身性炎症。尽管与炎症有关联,血栓在MKD中很少见或报道不足。我们的目标是报告不受控制的炎症作为缺血性卒中的原因的证据。
方法:病例报告。
结果:一名39岁的法裔加拿大患者因中风咨询。他报告了先前诊断为家族性地中海热,尽管有秋水仙碱预防,但自出生以来几乎每月都因复发性炎症发作而住院。攻击是由感染或压力引发的,持续了3-7天,包括高达41°C的发烧,疼痛的淋巴结病,腹痛,多关节痛和斑丘疹。中风导致了他最近的炎症发作。脑部MRI证实为急性梗塞,无慢性缺血性损伤。血液检查显示C反应蛋白升高,淀粉样蛋白A和免疫球蛋白D血栓前和自身抗体测试,头颈CT血管造影,超声心动图,心脏监测,和有毒的屏幕是不显著的。排除感染。他唯一的妹妹也有类似的攻击。在这两种情况下,32个自身炎症相关基因的测序确定了两个致病性甲羟戊酸激酶突变。他们的非血亲父母,同父异母的兄弟和四个孩子无症状。用抗白细胞介素-1β单克隆抗体治疗后,患者在超过4年内不再出现炎症发作或卒中.
结论:这位MKD患者在发作期间经历了缺血性卒中,归因于不受控制的炎症。研究排除了其他卒中病因。1岁前开始并持续>3天的反复发热发作,胃肠道症状,疼痛的淋巴结病,斑丘疹,触发器,口疮性口炎,非地中海血统,秋水仙碱预防无效与MKD一致。抗白细胞介素-1治疗可预防复发性自身炎症发作。
OBJECTIVE: Mevalonate kinase deficiency (MKD) is an autosomal recessive autoinflammatory disease characterized by recurrent systemic inflammation attacks. Despite interconnections with inflammation, thrombosis is rare or underreported in MKD. Our goal is to report evidence of uncontrolled inflammation as the cause of ischemic stroke.
METHODS: Case report.
RESULTS: A 39-year-old French-Canadian patient consulted for stroke. He reported a previous diagnosis of familial Mediterranean fever and hospitalizations nearly monthly since birth for recurrent inflammatory attacks despite colchicine prophylaxis. Attacks were triggered by infections or stress, lasted 3-7 days, and included fever up to 41°C, painful lymphadenopathies, abdominal pain, polyarthralgia and maculopapular rash. Stroke culminated his most recent inflammatory attack. Brain MRI confirmed an acute infarct, without chronic ischemic damage. Blood tests documented increased C-reactive protein, amyloid A and immunoglobulin-D. Prothrombotic and autoantibody tests, cervicocephalic CT-angiography, echocardiography, cardiac monitoring, and toxic screen were unremarkable. Infections were excluded. His only sister had similar attacks. In both cases, sequencing of 32 autoinflammatory-associated genes identified two pathogenic mevalonate kinase mutations. Their non-consanguineous parents, half-brother and four children were asymptomatic. Following treatment with anti-interleukin-1beta monoclonal antibodies, he no longer had inflammatory attacks or stroke in >4 years.
CONCLUSIONS: This MKD patient experienced an ischemic stroke during an attack, attributed to uncontrolled inflammation. Investigations excluded other stroke etiologies. Recurrent febrile attacks starting before age 1 and lasting >3 days, gastrointestinal symptoms, painful lymphadenopathies, maculopapular rash, triggers, aphthous stomatitis, non-Mediterranean ancestry, and ineffectiveness of colchicine prophylaxis are consistent with MKD. Anti-interleukin-1 therapy prevents recurrent autoinflammatory attacks.