Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.
系统性红斑狼疮(systemic lupus erythematosus, SLE)相关巨噬细胞活化综合征(macrophage activation syndrome, MAS)属于临床重症疾病, 病死率较高, 伴发神经精神症状少见, 在诊治过程中, 需积极判断患者出现的神经精神症状是由狼疮脑病(neuropsychiatric systemic lupus erythematosus, NPSLE)还是由巨噬细胞活化综合征引起。本研究回顾性分析2例就诊于华中科技大学同济医学院附属协和医院风湿免疫科伴神经精神系统病变的系统性红斑狼疮相关巨噬细胞活化综合征患者的临床资料。病例1为30岁女性, 2019年无诱因出现明显脱发, 伴消瘦、乏力、口干, 2021年3月腿软无力摔倒, 随后无明显诱因出现发热伴寒战, 完善相关检查后诊断为"系统性红斑狼疮", 给予激素、抗感染等对症治疗, 患者仍发热, 完善检查提示中度贫血, 铁蛋白升高, 甘油三酯升高, NK淋巴细胞活性减低, 穿孔素阳性率为4.27%, 诊断"噬血细胞综合征前期"; 2021年5月患者出现精神恍惚, 胡言乱语, 完善相关检查后诊断为"系统性红斑狼疮合并巨噬细胞活化综合征", 予甲泼尼龙、抗感染、改善精神状态等治疗后, 患者体温正常, 神经精神症状好转。病例2为30岁女性, 2019年6月出现颜面部鼻翼两侧蝶形红斑, 颈部数个红斑, 伴脱发、口腔溃疡、发热, 完善相关检查后诊断为"系统性红斑狼疮", 给予甲泼尼龙、静脉滴注人免疫球蛋白等治疗后病情缓解, 2019年10月患者出现神清淡漠, 无嗜睡, 并再次出现发热, 同时伴有头晕、呕吐, 完善相关检查提示中度贫血、NK淋巴细胞活性减低、甘油三酯升高、铁蛋白升高, 考虑诊断为"系统性红斑狼疮、狼疮脑病、巨噬细胞活化综合征", 予激素、静脉滴注人免疫球蛋白、抗感染、利妥昔单抗(美罗华)治疗, 患者病情好转出院, 出院后规律口服甲泼尼龙片, 精神症状仍间断发作; 2019年11月出现发热、躁狂、谵妄等精神症状, 后转为淡漠状态, 给予甲泼尼龙静脉滴注, 奥氮平片(再普乐)口服, 精神症状好转后给予利妥昔单抗治疗, 后因反复感染更换为贝利尤单抗, 在2021年3月患者精神异常症状恢复。通过分析临床症状、影像学检查、实验室检查、治疗经过及其效果, 推测病例1的神经精神症状由巨噬细胞活化综合征引起可能性大, 病例2的神经精神症状由系统性红斑狼疮引起可能性大。目前对两者的鉴别还缺乏直接的实验室依据, 可以通过临床表现、影像学表现、脑脊液检测、患者对治疗的反应来综合判断出现神经精神症状的病因, 本研究的2个病例最终取得较好的预后, 与对本病的早期诊断、治疗、干预密切相关。
Keywords: Hemophagocytic syndrome; Macrophage activation syndrome; Neuropsychiatric symptoms; Systemic lupus erythematosus.