Adult Onset Still’s Disease: Articular Manifestations in Twenty Cases

The adult onset Still’s disease is a rare inflammatory pathology of unknown pathogeny. The clinical features are variable. The diagnosis is difficult since exclusion of infectious, systemic and tumoral pathologies should be done. The articular complications are frequent and can be revelatory of this pathology. The articular prognosis depends on the diagnosis delay and the treatment efficiency. Our study aims to analyze different aspects of articular manifestations complicating adult onset Still’s disease to define epidemiological, clinical and evolving characteristics of these complications. It was a cross-sectional study concerning 20 cases of adult onset Still’s disease diagnosed from 1990 to 2015 in the internal medicine A department of Charles Nicolle Hospital in Tunis, meeting Yamaguchi criteria. We identified clinical, radiological, evolving and therapeutic profile of the articular manifestations occurred in these patients. There were 13 women and 7 men. The average age was 25 years. The arthralgias were reported in all cases;while, the arthritis interested fifteen patients. A hand deformation was found in four patients. A wrist ankylosis was noted in one case and a flexion elbow in one patient. The standard articular radiographs were normal in twelve cases. The treatment associated essentially non-steroidal anti-inflammatory and/or corticosteroids and/or methotrexate. Concerning the evolving profile, the monocyclic form was present in 25% of the cases, the intermittent form in 45% and the chronic articular form in 30% of our patients. The adult onset Still’s disease is rare and heterogeneous. The articular disturbances are frequent and have various outcomes.

Adult Onset Cerebral X-Linked Adrenoleuokodystrophy in 18 Cases

Adrenoleukodystrophy (ALD) is an X-linked inherited metabolic disease associated with the accumulation of very long chain fatty acids (VLCFA) in the nervous system, adrenal cortex, and testes. At least seven phenotypes can be distinguished, which are Addison only, childhood, adolescent and adult cerebral ALD, adrenomyeloneuropathy (AMN), and symptomatic or asymptomatic carriers. Children most often develop rapidly a progressive cerebral disease, whereas adults rarely develop a cerebral disease. The majority of adult-onset ALD patients are AMN. The prognosis of ALD remains unpredictable in individual patients. Family history can be very informative. The plasma VLCFA assay permits precise diagnosis. Specific changes on brain Magnetic Resonance Imaging (MRI) can have diagnostic utility. However, there is considerable overlap among adult-onset leukodystrophies. Adult onset form of cerebral X-linked ALD (AOCALD) is a rare disease. The disease progresses rapidly with widespread demyelination of the cerebral hemispheres. AOCALD is an important differential diagnosis for adults with psychiatric symptoms and progressive cognitive changes. In this article, we review on case reports of AOCALD.

Adult Onset Still’s Disease

The adult onset Still’s disease is a rare affection characterised by occurrence of fever, arthralgia or arthritis and evanescent cutaneous eruption. Multiple other systemic lesions make the diagnosis more difficult. Several diagnostic criteria were formulated to confirm this disease. The physiopathology of the adult onset Still’s disease is not well elucidated. However, several studies based on new facts in physiopathology, improved the therapy of refractory forms for which the biotherapy was an interesting alternative. The TNF alpha receptor antagonists are efficient on systemic and articular manifestations of this disease and allow a corticosteroid’s saving. Tocilizumab (interleukin 6 receptor antagonist), and Anakinra (interleukin 1 receptor antagonist) are also new promising treatments for resistant forms.

Prevalence of Myocilin Gene Mutation in Adult-Onset Primary Open Angle Glaucoma and Non-Glaucoma Subjects Who Are Indigenes of Rivers State, Nigeria

Background: Glaucoma is the leading cause of irreversible blindness incapacitating over 80 million people worldwide. Several pathogenetic mechanisms have been postulated to explain the optic nerve damage that occur in POAG among which genetic predisposition is prominent. Gene-Linkage-based studies have identified genes associated with POAG: Myocilin, Optineurin, WDR36, Tank-Binding Kinase (TBK1) and APbb-2. Objective: To investigate the prevalence of myocilin gene mutation in adult-onset POAG patients and non-glaucoma subjects who are indigenes of Rivers State. Methodology: In this comparative cross-sectional study, 393 POAG patients attending the Glaucoma Clinic of UPTH were compared with 393 age and sex-matched phenotypically normal participants. Clinical assessment combined with findings from clinical records was used. Venous blood was obtained for genomic analyses. Extracted DNA was sequenced with specific primers for myocilin and polymerase chain reaction. Zymo-Bead Genomic DNA kit protocol was used to detect allelic differences. Results: Total of 786 participants participated in the study. The mean age was 59.8 ± 11.8 years. The prevalence of myocilin gene mutation (MYOC) in the study population was 5.3%, in the POAG group was 8.4%, and 2.3% in the non-glaucoma group. This observed difference was statistically significant (p = 0.001). Location of the mutant myocilin gene was in GLC1A 171638779, 171638703, 171638610 and 171638608. Conclusion: Mutations in myocilin gene are associated with adult-onset POAG in Rivers State. Its relevance as a biomarker for diagnosis of adult-onset POAG needs further investigations.

Successful treatment of adult-onset still disease caused by pulmonary infection-associated hemophagocytic lymphohistiocytosis: A case report

BACKGROUND Adult-onset still disease(AOSD) and hemophagocytic syndrome(HPS) are two inflammatory diseases with very similar clinical manifestations. HPS is one of the most serious complications of AOSD and its risk of death is very high. It is difficult to identify HPS early in patients with AOSD, but early identification and proper treatment directly affects the prognosis.CASE SUMMARY A 39-year-old male showed a high spiking fever and myalgia. Laboratory data revealed elevated white blood cell, serum ferritin, and neutrophil percentage.However, his fever failed to relieve after a clear diagnosis of AOSD caused by pulmonary infection and treatment by antibiotics and corticosteroids;further laboratory data showed elevated serum ferritin, C-reactive protein, erythrocyte sedimentation rate and triglyceride, as well as liver abnormalities. Bone marrow smear showed hemophagocytosis. Secondary HPS was definitely diagnosed. The high fever disappeared and the laboratory findings returned to normal values after treatment by high-dose intravenous methylprednisolone and methotrexate.CONCLUSION For AOSD patients with high suspicion of HPS, active examination needs to be considered for early diagnosis, and timely using of adequate amount of corticosteroids is the key to reducing risk of HPS death.

Identification of novel biomarkers for adult-onset-immunodeficiency(AOID)syndrome using serum proteomics

Objective:To identify the candidate protein biomarkers of adult-onset-immunodeficiency(AOID) syndrome using serum proteomics. Methods:Screening and verification phases were performed in the study. A total of 97 serum samples were classified into three groups:AOID patients with opportunistic infections(active AOID),AOID patients without opportunistic infections(inactive AOID),and healthy control. In the screening phase,pooled sera collected from patients and healthy control in each group were separated by 2D-gel electrophoresis,analyzed for differentially expressed proteins and identified for biomarkers using LC/MS. In the verification phase,the protein candidates were selected for confirmation by western blotting. Results:The analysis revealed 35 differentially expressed proteins. Three proteins including haptoglobin,gelsolin,and transthyretin,were selected for verification. The results showed that the levels of haptoglobin in both active and inactive AOID groups were significantly higher than that in the control group,while the levels of gelsolin in the active AOID group were significantly lower than that in the inactive AOID group. The level of transthyretin in the active AOID group was also significantly lower than that in the control group. Conclusions:The comparison of serum proteins between the three groups revealed three candidates which are related to chronic inflammatory diseases. Haptoglobin and transthyretin biomarkers could be applied in clinical assessment for monitor of disease outcome,including for the study of AOID pathogenesis.

Study of Tripterygium Associated with Nicotinamide in Treating Late-onset Autoimmune Diabetes Mellitus in Adults

Objective: To explore the effect of Tripterygium polyglycoside (TP) associated with nicotinamide on the islet cell function, immune parameters and lipoperoxide (LPO) in adult patients with late-onset autoimmune diabetes mellitus (LADA). Methods: Thirty-six cases of LADA were randomly divided into three groups: TP group (n=12), treated with TP plus orally taken metformin; combined treatment group (n= 12), treated with TP combined with nicotinamide and metformin, and control group (n=12) treated with metformin alone. They were followed-up for 18 months. Results: (1) Compared with the control group after 9 months of treatment, postprandial plasma glucose and LPO in combined treatment group were decreased (P <0.05), and the postprandial C-peptide was higher (P<0.05). At the 18th month, the value of postprandial C-peptide in the TP and combined treatment group was higher than that in the control group. The slL-2R level of both TP and combined treatment groups were lowered (P<0.01); (2) Islet cell antibody (ICA) positive of 5 cases in the TP group and 6 cases in the combined treatment group got converted to the negative respectively , while only one in the control group at the time (P<0.05); (3) The level of LPO in the combined treatment group was significantly lower than that in the TP group at the 18th month of treatment (P<0. 05). Conclusion: TP combined with nicotinamide played a role in immunity regulation, decreasing the titer of islet cell antibody and slL-2R, which also reduced the production of LPO and had a tendency to improve islet cell function in early LADA patients.

王振亮运用四逆汤治疗成人斯蒂尔病经验

成人斯蒂尔病是一种多因素参与的自身炎症性疾病,以发热、皮疹、关节疼痛和多器官受累为特点,目前尚无根治办法。西医治疗以非甾体类抗炎药、糖皮质激素、免疫抑制剂及生物制剂治疗为主。王振亮教授认为阳虚寒凝血瘀是成人斯蒂尔病核心病机,临床表现以阴阳不和、寒凝血瘀为主,也常夹湿、郁热,病位在半表半里,病性寒热错杂,以温阳益气立法,以四逆汤为核心方,同时重视顾护脾胃以及治血药的运用,谨守病机随证配伍,灵活运用。

LMNB1相关常染色体显性遗传成人型脑白质营养不良家系分析

目的总结一个LMNB1相关常染色体显性遗传成人型脑白质营养不良(adult-onset autosomal dominant leukodystrophy,ADLD)家系的临床、影像学特点,并进行致病性变异分析。方法选取2023年11月首都医科大学宣武医院确诊为ADLD患者1例,收集先证者及家系其他患者的临床和影像学资料,对先证者进行全外显子组测序分析及LMNB1基因的多重连接探针扩增(multiplex ligation-dependent probe amplification,MLPA)检测,并进行致病性分析和表型匹配分析。结果本例患者(先证者)男,44岁,因“大小便障碍3年,双下肢乏力2年余”就诊,基因检测示LMNB1基因1-11号外显子重复变异,评定为致病性变异,表型与ADLD匹配,先证者(Ⅲ:9)和Ⅲ:6以自主神经功能障碍起病,系ADLD典型表现,Ⅱ:11首发症状为头部震颤,与其他患者不同。结论ADLD患者的LMNB1基因1-11号外显子重复变异,符合常染色体显性遗传方式。成年患者以自主神经功能障碍起病,随后累及小脑、锥体束,MRI示广泛对称的脑白质病变、脊髓萎缩时应考虑ADLD,建议行LMNB1基因检测。

CSF1R基因突变致ALSP发病研究进展

成人发病的白质脑病合并轴索球样变和色素性胶质细胞(adult-onset leukoencephalopathy with axonal spheroids and pigmented glia,ALSP)是临床罕见的常染色体显性遗传病,其具体的发病机制目前还未明确。集落刺激因子1受体(colony-stimulating factor 1 receptor,CSF1R)是一种细胞表面跨膜酪氨酸激酶受体,与其相关的编码基因突变已被证实是ALSP的潜在致病因素。然而,目前关于CSF1R基因突变致使ALSP发病的具体机制尚不清楚。本文回顾CSF1R基因在ALSP发病过程中的突变位点及致病机制研究,发现CSF1R突变可以通过显性负性效应、功能丧失、单倍体剂量不足及功能获得等机制导致小胶质细胞功能异常,进而引起ALSP的发病。对ALSP病因的深入认识有助于更好地探索潜在的治疗方法。

线粒体丙氨酰t-RNA合成酶2基因突变相关的脑白质病1例及文献回顾

线粒体丙氨酰t-RNA合成酶2(alanyl-transfer RNA synthetase 2,AARS2)基因突变相关的脑白质病(AARS2 leukoencephalopathy,AARS2-L)是一种罕见的迟发性脑白质营养不良,文献报道仅32例。本文报道1例44岁女性患者进行性认知障碍下降、精神行为异常5年,同时合并卵巢功能衰退;头部磁共振成像显示双侧大脑半球广泛的白质脱髓鞘;基因全外显子测序发现AARS2基因复合杂合突变(c.179 C>A和c.2752 C>T),结合临床特征该患者被诊断为AARS2-L。同时,对目前已报道的AARS2-L病例的临床特征和基因表达特点等进行了回顾与分析。

健脾清热除湿汤治疗成人发病型特应性皮炎经验

成人发病型特应性皮炎指患者发病年龄大于等于18岁的特应性皮炎,其临床表现与婴儿期、儿童期特应性皮炎有所不同,适应的诊断标准也不同,近年来逐渐受到重视。宋业强教授结合多年临床经验,提出脾虚湿热是成人发病型特应性皮炎的关键病机,并自拟健脾清热除湿汤治疗该证型患者,取得了很好的临床效果。文章以验案为例,介绍成人发病型特应性皮炎的相关内容。

成人斯蒂尔病与其他不明原因发热疾病的鉴别诊断指标

目的探讨成人斯蒂尔病(AOSD)与其他不明原因发热(FUO)疾病的鉴别诊断指标。方法收集2010年1月-2021年5月在陆军军医大学第一附属医院住院的177例AOSD患者及163例待鉴别FUO患者的临床资料及实验室指标,随机分为训练组及验证组。通过单因素分析提取有统计学意义的变量进行受试者工作特征(ROC)曲线分析并获取变量的最佳截断值,进一步通过多因素logistic回归分析筛选出具有鉴别诊断意义的指标,并构建列线图模型;采用ROC曲线、校准曲线及决策曲线分析列线图的准确性及稳定性。结果单因素分析结果显示,4项临床特征(关节痛、皮疹、咽痛、肌痛)及14项实验室参数[白细胞计数(WBC)、单核细胞百分比、中性粒细胞百分比、淋巴细胞百分比、血小板计数、C反应蛋白、白细胞介素-6(IL-6)、铁蛋白、球蛋白、免疫球蛋白A、免疫球蛋白G(IgG)、肌酸激酶、肌酐、补体C3]差异均有统计学意义(P<0.05)。多因素分析结果显示,关节痛、WBC≥9.995×109/L、IL-6≥98.13ng/L、铁蛋白≥507.37ng/ml、球蛋白≤36.58g/L、IgG≤13.59g/L、补体C3≥1.27g/L均与AOSD相关(P<0.05)。训练组及验证组的曲线下面积(AUC)分别为0.917[95%可信区间(95%CI)0.883~0.951]、0.869(95%CI0.802~0.936);校准曲线表现出良好的一致性;决策曲线分析表明,训练组及验证组分别在5%~85%、10%~85%广大风险范围内显示出较大的正向收益率。结论该研究建立起一个相对准确的AOSD鉴别诊断模型,关节痛、WBC、IL-6、铁蛋白、球蛋白、IgG及补体C3多指标联合应用有助于鉴别AOSD与其他FUO病因。

成人斯蒂尔病发病机制及相关临床特征的研究进展

成人斯蒂尔病是一种少见的、病因尚不明确的全身性自身炎症性疾病,其具有临床症状表现复杂而不典型、缺乏统一有效的相关检查以辅助诊断、临床治疗效果差异性大等特点,在临床上通常难以明确诊断并给予规范化治疗。目前关于成人斯蒂尔病发病机制的研究方向较多,本文结合相关文献总结以上研究成果,供后续相关科研工作参考。

系统性红斑狼疮及成人Still病合并巨噬细胞活化综合征的临床特点及诊断指标

目的:分析和比较系统性红斑狼疮(systemic lupus erythematosus,SLE)和成人Still病(adult-onset Still’s disease,AOSD)合并巨噬细胞活化综合征(macrophage activation syndrome,MAS)患者的临床及实验室指标特点,评估已有的2016年欧洲抗风湿病联盟/美国风湿病学会/儿童风湿病国际试验组织发布的全身型幼年特发性关节炎(systemic juvenile idiopathic arthritis,sJIA)合并MAS(sJIA-MAS)分类标准在不同自身免疫病背景下的适用情况,并提出新的诊断预测指标,为提高MAS早期诊断率、改善患者预后提供参考。方法:回顾性分析2000—2018年在北京大学人民医院住院的24例SLE合并MAS患者和24例AOSD合并MAS患者的临床及实验室数据,分别与同期未发生MAS的50例SLE及50例AOSD患者进行比较,通过受试者工作特征(receiver operating characteristic,ROC)曲线确定预测MAS的实验室指标截断值。进一步使用实验室诊断预测值对2016年sJIA-MAS分类标准进行改进,探讨改进后的标准对于AOSD合并MAS的适用性。结果:约60%的SLE合并MAS及40%的AOSD合并MAS患者发生在原发病确诊后的3个月内。发热是MAS最常见的临床表现。实验室指标除了2004年国际组织细胞学会修订的噬血细胞综合征诊断标准中的指标外,MAS患者的天冬氨酸转氨酶及乳酸脱氢酶也显著升高,白蛋白显著下降,噬血现象仅见于约50%的MAS患者。ROC曲线分析显示,当SLE患者铁蛋白≥1010μg/L、乳酸脱氢酶≥359 U/L,AOSD患者纤维蛋白原≤225.5 mg/dL、甘油三酯≥2.0 mmol/L时,对MAS诊断有最好的区分价值。将2016年sJIA-MAS分类标准应用于AOSD合并MAS,诊断的敏感性和特异性分别为100%和62%,对其中特异性低的铁蛋白和纤维蛋白原条目进行改进,诊断特异性可升高为86%。结论:SLE合并MAS及AOSD合并MAS最常发生于疾病确诊后的早期,不同疾病继发MAS因受自身免疫病特点的影响而在实验室指标方面存在明显差异,以同一标准进行MAS诊断可能导致误诊或漏诊。2016年sJIA-MAS分类标准在AOSD合并MAS诊断中敏感性高而特异性低,对之进行改进可提高特异性。

国医大师卢芳辨治成人斯蒂尔病发热经验

[目的]总结卢芳教授治疗成人斯蒂尔病(adult-onset Still’s disease,AOSD)发热的临床经验。[方法]通过临床跟师、记录医案及查阅文献,从理论来源、辨证思路、治则治法、方剂中药四个层面总结卢老治疗AOSD的临床经验,并附医案佐证。[结果]卢老认为,AOSD以发热为主要症状,且发热具有明显的节律性,热退则诸症缓解。卢老指出,AOSD病机为脏腑功能失衡,阴阳不谐而致发热,当以恢复脏腑的正常功能及气血阴阳平衡为要,故根据多年临证经验,总结出以发热为辨证论治的中心,按患者发热时间确定基础方,根据其他症状加减用药的中医综合诊疗方法。文中所举验案卢老辨证为湿热蕴结证,以三仁汤加减治疗,上举清阳、下利湿热,恢复气机的正常运行,则热退而诸症缓解。[结论]卢老以发热为中心辨治AOSD,强调辨病与辨证相结合,根据患者症状加减用药,在临床取得了稳定的疗效,丰富了AOSD的辨证论治体系,便于临床应用及推广。

Jaundice in Adult in-Patients at a Tertiary General Hospital

Objective: The aim of the study is to investigate the “new-onset jaundice” incidence, map of causes, approaching method, and risk factors for treatment failure in adult in-patients at a tertiary general hospital as Cho Ray Hospital, Ho Chi Minh City, Viet Nam. Method: Retrospective study was done on 416 jaundice patients administered over 38 continuous days. Laboratory tests investigated were total bilirubin, direct bilirubin, AST, ALT, AST/ALT ratio, GGT, AP, bilirubin and urobilinogen in urine. Jaundice was defined as total bilirubin ≥ 2.5 mg/dL, direct bilirubin jaundice defined as direct bilirubin > 2 mg/dL and D/T percentage > 60%, the severity of AST, ALT evaluated according to Common Terminology Criteria for Adverse Events, AST/ALT ratio, and bilirubin, urobilinogen in urine. Outcome of treatment were classified in two groups: failure (dead or discharge due to worse status) and success. Descriptive statistics and analytic statistics were applied, mono-variable analysis and multinomial logistic regression to find out the independent risk factors for treatment failure. Results: The incidence of “new-onset” jaundice in adult patients was 11 ± 5 person/day. The map of jaundice included 3 phases as pre-heaptic 13.7%, in-hepatic 58.2%, and post-hepatic 22.8%. Pancreatic and biliary tract diseases accounted 17.1%, then cirrhosis 16.3%, liver tumor 14.7%, hepatitis 8.9%, sepsis 8.9%, hematology diseases 7.9%, and cardiac diseases 7.5%. A guide for approaching causes of jaundice basing on 7 parameters as total bilirubin, D/T percentage, severity of ALT, AST/ALT ratio, severity of GGT, and bilirubin and urobilinogen in urine was established. The overall mortality was 7.5% (31/416), sepsis had highest death rate of 37.8% (14/37). Sepsis and AST/ALT ratio > 2 were the two independent risk factors of mortality. Conclusion: At tertiary hospital, jaundice is common sign in adult patient, diverse enormously in many clinical wards. The map of causes of jaundice completed all 3 phases: pre-hepatic, intra-hepatic and post-hepatic phase. Drug hepatitis jaundice was an important cause in hepatitis. Sepsis had highest mortality in adult jaundice patients. Combination of 7 criteria as total bilirubin, the D/T percentage, ALT severity, AST/ALT ratio, GGT, bilirubin and urobilinogen in urine gave the guide for approaching to jaundice. Sepsis and AST/ALT ratio > 2 were independent risk factors of treatment failure. The survey of jaundice in adult in-patients in a tertiary general government hospital gave the full picture for this common pathological sign.

国医大师朱良春治疗成人斯蒂尔病的经验

成人斯蒂尔病(adult-onset Still’s disease, AOSD)是一种自身免疫性疾病,其证候多变,病机复杂,属于罕见之病。根据AOSD关节炎和(或)关节痛等临床表现,中医学将AOSD归属于“痹病”范畴。国医大师朱良春认为痹病具有“久病多虚、久病多瘀、久病入络、久病及肾”这一共同核心病机,在此基础上创立自拟方痹通汤。临床上,朱良春教授灵活运用痹通汤加减治疗诸多疑难杂症,均取得显著疗效,充分发挥了中医药的优势。将朱良春教授运用痹通汤加减治疗AOSD的经验加以总结,以期为临床开辟新思路,提供新方法。

表现为持续性瘙痒性斑块的成人Still病一例

患者,女,58岁。全身持续性瘙痒性斑块伴发热20天。血清铁蛋白增高,血常规白细胞、中性粒细胞升高,肝功能异常,脾大。皮损组织病理示:棘层中上部见角化不良细胞,真皮浅层血管周围见淋巴细胞和嗜酸粒细胞浸润。诊断:成人Still病。予糖皮质激素及甲氨蝶呤治疗,病情好转。

成人斯蒂尔病1例

成人斯蒂尔病起病原因及发生机制仍不清楚,临床主要表现为发热、关节痛、皮疹,且有白细胞、血清铁蛋白等指标增高,但缺乏针对该病的特定诊断指标,导致临床漏诊、误诊比率较高。通过查阅相关文献,发现本病内镜下报道资料较少。本文就1例成人斯蒂尔病病例及胃镜下表现进行报道,并结合AOSD相关诊断指标、治疗方面的最新进展进行归纳,旨在为临床诊疗本病寻求更精准的选择。