强直性脊柱炎2218例临床资料分析及中医证候研究

【作者】 马骁；

【导师】 阎小萍；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2009， 博士

【摘要】 研究目的:强直性脊柱炎(Ankylosing Spondylitis,AS)是一种以中轴关节慢性炎症为主的全身性、免疫性疾病。由于患者的早期症状常早于骶髂影像学改变5-7年出现,而且目前普遍采用的1984年修订的纽约标准不利于AS早期诊断,大部分患者在确诊时已失去了治疗的良好时机。早期诊断、及时治疗已成为当务之急。本研究对导师阎小萍教授自2006年至2009年诊治的2218例AS患者进行临床资料分析,以期发现利于AS早期诊断的因素,为AS的早期诊治提供线索和依据。目前,对AS的证候分类仍未统一,从而一定程度上阻碍了该病的中医药规范化辨证施治,进一步影响了中医整体疗效的提高。导师阎小萍教授长期以来运用中医辨证施治的特色诊治AS,并将之归属为中医病名“大偻”临床上积累了丰富的实践经验,取得了良好的治疗效果。本研究采用四诊合参的传统中医辩证思路结合现代数理统计的方法,以初步探讨AS中医基本证候分布情况,验证导师临床证候分类的可行性,同时对AS中医证候的研究方法进行初步探讨,采用聚类分析、主成分分析对AS的中医证候要素进行归纳和提取,为AS中医诊断标准的建立、证候分类的完善打好基础工作,为AS的防治提供参考依据。对进一步总结导师学术思想的科学内涵具有重要的实际意义。方法:本研究应用前瞻性调查研究方法,采用Epidata3.02数据库进行数据管理,在SPSS12.0软件平台进行数据统计分析。AS临床资料分析采用描述性频数分析、独立样本t检验、卡方检验、相关性分析;证候学研究采用传统中医辨证方法与现代Logistic回归、聚类分析、主成分分析等方法,深入系统研究AS的临床特点、证候特点。结果:临床特点:AS男女发病比例为3.28:1,平均发病年龄为22.18±8.10岁,其中男性平均发病年龄为21.20±7.80岁,女性平均发病年龄为25.44±8.21岁,女性发病年龄明显晚于男性患者4年,且女性AS幼年发病比率为9.07%明显低于男性AS患者幼年发病比率(25.59%)。AS患者HLA-B27的阳性率为86.94%,女性AS患者携带HLA-B27的比率明显低于男性AS患者,仅为75.10%。46.88%的AS患者发病时有明确的诱发因素,因感受风邪、寒冷、潮湿而发病的占26.06%,因外伤而导致发病的占8.12%,因剧烈运动导致发病的占3.92%,因劳累诱发疾病者占4.10%。AS累及范围广泛,以腰骶、脊背最为常见,其次为髋关节、膝关节和颈项、肩、腹股沟、胸肋、踝关节等。34.13%的AS患者出现过关节的肿胀,主要为膝、踝等四肢大关节。幼年发病的AS患者出现关节肿胀的几率明显高于成年发病的AS患者。前葡萄膜炎是AS容易伴发的关节外病变,本研究出现过前葡萄膜炎的AS患者占16.19%,且男性与女性并发率比较无显著性差异。AS被延误诊断平均年限为5.30±5.75年,误诊、漏诊率达88.82%,JAS的误诊率高达92.17%,明显高于成年发病组,同时发现性别对AS的误诊年限和误诊比率无明显影响,而阳性家族史的AS患者的平均误诊年限明显短于无AS家族史的患者,HLA-B27阴性的AS患者的误诊率明显高于HLA-B27阳性患者。AS常被误诊的疾病主要与腰椎间盘突出、类风湿性关节炎和腰肌劳损相关。女性AS患者的枕墙距、颌柄距、指地距、Schober试验、脊柱活动度均明显轻于男性AS患者;未携带B27基因的AS患者脊柱活动受限程度均明显轻于携带HLA-B27的AS患者;而发病年龄对颈部、腰部、脊柱的活动度影响不大。AS伴发心电图异常的比率为7.45%,AS髋关节受累发生率为57.09%,且男性AS患者的髋关节受累率明显高于女性患者;HLA-B27阳性AS患者髋关节的受累率明显高于HLA-B27阴性患者;幼年发病的AS患者髋关节受累率高于成年发病的患者;家族史对AS患者髋关节的受累率无明显影响。本研究骨量减少和骨质疏松的发生率占AS患者的54.45%,且男性患者的腰椎和股骨骨量减少、骨质疏松的发生率均明显高于女性患者。男性AS患者骶髂关节炎Ⅱ级改变者占26.71%、Ⅳ级占30.71%,女性AS患者骶髂关节炎Ⅱ级改变者占47.68%、Ⅳ级占10.23%。HLA-B27阴性的患者骶髂关节炎Ⅱ级改变的比率明显高于HLA-B27阳性的患者,Ⅳ级改变的比率明显低于HLA-B27阳性患者。证候研究:AS中医症状出现的频次依次为:倦怠乏力、腰膝酸软、畏寒喜暖、晨僵、夜寐不安、盗汗、自汗、四末不温、口渴喜饮、胸胁憋闷、大便稀溏、驼背畸形、心烦易怒、面色无华、气短、男子阴囊寒冷或女子白带寒滑、心悸、手足心热、眩晕耳鸣、小便清长、发热、大便干结、口苦粘腻、恶热喜凉、目睛红赤、小便短赤。舌质出现的频次依次为舌暗淡、舌淡红、舌边尖瘀斑瘀点、舌胖嫩边有齿痕、舌下脉络瘀曲、舌紫暗、舌边尖红等,舌苔出现的频次依次为薄白苔、薄黄苔、白腻苔、黄白相兼腻苔等,脉象出现的频次依次为脉沉、细、弦、尺弱、滑、数等。中医证型所占百分比例为肾虚督寒证55.82%、邪痹肢节证18.44%、邪郁化热证13.07%、邪及肝肺证10.60%、湿热伤。肾证2.07%。通过非条件Logistic回归建立AS中医证候预测模型,腰骶痛、腰部冷感、脊背痛、臀部痛、腰椎活动受限、畏寒喜暖、四末不温、面色无华、小便清长、薄白苔、舌下脉络瘀曲、脉细、脉沉、脉弦为肾虚督寒证证候诊断的主要成分;发热、口苦粘腻、恶热喜凉、踝关节热感、遇冷则舒、小便短赤、舌紫暗、苔黄腻对湿热伤肾证证候诊断的贡献率较大;腰部冷感、大腿肌肉痛、腹股沟痛、髋关节痛、膝关节痛、舌瘀斑瘀点是邪痹肢节证的证候诊断要点;邪及肝肺证的证候组成要素为心烦易怒、胸胁憋闷、眩晕耳鸣、目睛红赤、心悸、眼痛干涩、胸痛;发热、恶热喜凉、心烦易怒、大便干结、小便短赤、口渴喜饮、眼痒多眦、暗淡舌、舌边尖红、腹股沟痛、髋关节痛、膝关节痛、膝关节肿胀、遇冷则舒为邪郁化热证的诊断要点,且五个证型中除邪痹肢节证外其它四个证型的预测模型诊断正确率均大于90%。通过系统聚类方式证实AS临床可分为5类,且此5类恰与导师阎小萍教授临床辨证相符。通过主成分分析得出:邪及肝肺证:特异症状为胸痛、胁肋疼痛、胸胁憋闷、气短、目睛红赤,主要症状为眩晕耳鸣、舌瘀斑瘀点,次要症状为髋关节痛、腹股沟痛、舌紫暗、脉弦等;邪痹肢节证:特异症状为膝关节痛,主要症状踝关节痛、足跟痛,舌淡红,次要症状为上肢关节疼痛等;肾虚督寒证:特异症状为畏寒喜暖,主要症状为四末不温、腰骶痛、颈项痛、腰膝酸软、驼背畸形、小便清长、舌暗淡、薄白苔,次要症状为大便稀溏、尺脉弱、脊背疼痛、夜间加重、脉沉、臀部深处痛、男子阴囊寒冷或女子白带寒滑、白腻苔等;湿热伤肾证:特异症状为口苦粘腻,主要症状为舌边尖红、苔黄腻、脉滑,次要症状为手足心热等;邪郁化热证:特异症状为关节红肿热痛,主要症状为发热、恶热喜凉、大便干结、小便短赤、薄黄苔、脉数,次要症状为晨僵、心悸、舌下脉络瘀曲、黄白相兼腻苔、脉细等。结论:本研究通过对2218例AS患者临床资料较为全面的分析,提高了对该病临床特点的认识,提示要重视AS发病年龄更加年轻化的趋势;重视男性AS患者的幼年发病比例;重视女性AS患者HLA-B27的阴性比例;重视AS首发部位的分布特点和外周关节病变;重视AS的髋关节受累情况及骨质疏松的发生率等。通过对导师临床辨证AS活动期的五类证候进行Logistic回归分析,建立辨证预测模型检验,除邪痹肢节证临床预测正确率为83.2%,其余四个证型的临床预测正确率均大于90%,提示辨证预测模型适合临床推广使用,提高临床的可操作性。本研究采用聚类分析对AS的中医证候要素进行客观化的归纳、分类,避免了对辨证主观化判断的缺陷,聚类分析结果与老师临床证候分类基本吻合,说明导师临床证候分类有着很高的客观性与现实性,值得进一步推广。利用主成分的载荷数对AS中医证候进行量化评估,使得中医证候中的症状更加简化、量化,便于临床的辨证分类。聚类分析结合主成分分析达到了临床对AS中医证候要素归纳和提取的目的,值得进一步深入研究及推广应用。更多还原

【Abstract】 Objective:Ankylosing spondylitis(AS) is a systemic,autoimmune disease,mainly with chronic inflammation of axial joints,characterized by almost all involved for the sacroiliac joints.AS not only often happens in and around the intervertebral disc annulus fibrosus ligament calcification and bony ankylosis,but also involves peripheral joints,heart,lung, kidney,eye,nerve,muscle and other organs.The early symptoms of patients often appear as early as the Sacroiliac image changes 5-7 years,and the diagnostic criteria now used is New York Criteria revised in 1984,which means the patients meeting standard are with advanced AS and have lost good opportunity to treat.Early diagnosis and timely treatment has become a top priority.In this study,2218 confirmed case are retrospective analyzed,which are treated by Professor Yan Xiaoping from 2006 to 2009,to find the distinguishing features of ealy diagnosis.There is no appropriate technical term of AS in Traditional Chinese medicine.AS is categories in BI disease approximately.At present,the classifications of AS-type are not yet unified,which hinder the Chinese medicine treatment to some extent.Professor Yan Xiaoping cures AS by traditional Chinese medicine Differential Treatment in long-term,and categories AS in DALV term.She accumulates plenty of practical experience and acquires good therapeutic effect.This study combines the use of four diagnostic parameters of the dialectical thinking of traditional Chinese medicine with modern methods of mathematical statistics to preliminary explore the AS TCM syndrome distribution,of basic,scientific,objective clinical instructors to verify the feasibility of Syndromes,established ankylosing spondylitis Differentiation Syndrome and the main elements of the diagnostic criteria for AS the establishment of Chinese medicine,syndrome differentiation type of work to lay a solid foundation of sound for the AS to provide reference for the prevention and treatment. Instructors for further academic thought summed up the scientific connotation of great practical importance.Methods:This study usd the forward-looking research method,by using the Epidata 3.02 data base,analyzed by SPSS12.0.Clinical data were analyzed by Descriptive analysis of frequency,Independent samples t test,Chi-square test,Correlation Analysis.Syndrome study was analyzed by Dialectical method of traditional Chinese medicine,modern Logistic regression,cluster analysis and principal component analysis.Results..AS male and female incidence ratio of 3.28:1,with an average onset age of 22.18±8.10 years old,women age at onset significantly later than male patients and female incidence ratio of childhood AS was significantly lower than male patients.AS patients with HLA-B27 positive rate of 86.94%for female patients with AS carry HLA-B27 was significantly lower than the ratio of male patients with AS,only 75.10%.There are 46.88%of AS patients have a clear predisposing factor,because of the feelings of wind,cold,wet and lead to diseases accounted for 26.06%,due to trauma caused by the total incidence of 8.12%,due to strenuous exercise resulted in the incidence accounting for 3.92%,fatigue lead to diseases,accounting for 4.10%.Involved a wide range of AS to lumbosacral,back the most common,followed by hip,hip deep,knee and neck,shoulder,groin,sternum,ribs,ankle and so on.34.13%of AS patients have joint swelling,mainly for the knee,and ankle joints,such as large limbs.AS childhood morbidity in patients with joint swelling was significantly higher than the probability of AS in patients with adult onset.AS iridocyclitis is easily associated with extra-articular lesions,the study of AS patients with iridocyclitis had accounted for 16.19%of the patients,and complicated by the rate of men and women showed no significant difference. AS diagnosis was delayed for an average period of 5.30±5.75 years,the misdiagnosis rate was 88.82%,JAS misdiagnosis rate of 92.17%,significantly higher than the adult onset group. The misdiagnosis of gender on the AS number of years and no significant effect on the rate of misdiagnosis,and positive family history of AS patients was significantly shorter average length of misdiagnosis in patients with non-AS family history,HLA-B27 negative AS patients with HLA misdiagnosis rate was significantly higher than that -B27-positive patients. AS is often misdiagnosed as lumbar disc herniation,rheumatoid arthritis,and diseases such as lumbar muscle strain.The occipital-wall distance,stem from the jaw means to distance, Schober test,spinal activity of female patients with AS was significantly better than male patients with AS;B27 gene does not carry spinal activity limitation in patients with AS were significantly better than to bring the level of HLA-B27 The AS patients;and the pathogenesis of age on the neck,waist,spine little effect on the activity.AS associated with the rate of abnormal ECG was 7.45%,abdominal B-abnormal ratio of 24.62%.AS the incidence of hip involvement was 57.09%,and male AS patients with hip involvement was significantly higher than female patients;HLA-B27 positive AS patients with the affected hip was significantly higher than that in patients with HLA-B27 negative;childhood morbidity in patients with AS higher than the rate of hip joint involvement in patients with adult onset; family history of AS in patients with the affected hip was no significant impact.In this study, bone mass and reduce the incidence of osteoporosis in patients with AS accounts for 54.45%, and male patients with lumbar and femoral bone mass reduction in the incidence of osteoporosis were significantly higher than female patients.AS male patients with gradeⅡsacroiliitis change accounted for 26.71%,Ⅳ-class accounting for 30.71%of female patients with AS levelⅡsacroiliitis change accounted for 47.68%,Ⅳ-class accounting for 10.23%. HLA-B27 negative patients with gradeⅡsacroiliitis was significantly higher than the rate of change in HLA-B27-positive patients,Ⅳlevel was significantly lower than the rate of change in HLA-B27 positive patients.Syndrome research:the frequency of TCM symptoms for AS were:fatigue fatigue, weakness in the knee waist,hi chills warm,morning stiffness,disturbed sleep soundly the night,sweating,spontaneous,four at the end of non-temperature,hi drink thirst,chest rib Inter-feel oppressed,thin stool soft,humpback deformity and upset irritability,not shiny face, shortness of breath,man or woman scrotum cold winter leucorrhea Waterloo,palpitations,hot hand-foot-heart,dizziness ringing in the ears,a long clearance urine,fever,dry stool,pain stick greasy,evil hot-hi cold eye red red heads,short red urine.Tongue pulse frequency appears bleak followed by the tongue,tongue ecchymosis blood,the tongue side of a similar fat teeth tender to bite marks,light red tongue,sublingual blood Mailuoning Qu,dark purple tongue,red tongue tip side,crack the tongue,bright red tongue,tongue atrophy,thin white coating,thin yellow moss,white greasy moss,greasy moss and with yellow and white,yellow greasy moss,moss thick white,yellow thick moss,moss,or spend less peeling moss,pulse Shen,small,string,feet weak,Waterloo,Mathematics,Shibuya,ease.According to constituent ratio of classification of syndromes due to TCM,there were 55.82%cases with syndrome of deficiency in kidney and Du Channel with cold manifestations cases with syndrome of obstruction in joints attacked by pathogenic factors accounting for 18.44%, syndrome of pathogenic factors encroaching on the Liver and the Lung accounting for 13.07%,with syndrome of accumulated pathogenic factors transforming into fire accounting for 10.60%,and syndromes of impairment of kidney by damp-heat accounting for 2.07%.Lumbosacral pain,chills warm hi,four at the end of non-isothermal,dizziness ringing in the ears,runny stool thin,urine-ching Cheung,sublingual blood Mailuoning Qu,thin white coating,small pulse,Shen pulse,the pulse string for deficiency in kidney and Du Channel with cold designate the main symptoms of the diagnosis.Fever,Bitter and viscous mouth feel, fear of heat,like cold,dizziness ringing in the ears,runny stools soft,palpitations,thick and greasy coating of white,thick and greasy yellow coating on impairment of kidney by damp-heat Syndrome higher contribution rate of diagnosis;Hip pain,knee pain,waist apathy, back pain,thigh muscle pain,groin pain,aggravating the cold face is obstruction in joints attacked by pathogenic factors permit diagnosis;pathogenic factors encroaching on the Liver syndrome elements for the upset irritability,chest and threatened the two feel oppressed,chest pain,neck pain,dizziness ringing in the ears,eyes red head red,dry eye pain,exfoliative moss; Fever,bad cold-hi heat,sweating,dry stool,urine short,hi thirsty drink,lumbosacral pain, groin pain,knee swelling for accumulated pathogenic factors transforming into fire of the diagnosis.And the five card-based diagnostic accuracy rate of prediction models are more than 90%.Way through the system confirmed that AS clustering can be divided into 5 clinical categories,corresponding to mentor Professor yanxiaoping evil Syndrome Differentiation and syndrome of pathogenic factors encroaching on the Liver and the Lung,syndrome of obstruction in joints attacked by pathogenic factors,syndrome of deficiency in kidney and Du Channel with cold,syndromes of impairment of kidney by damp-heat,syndrome of accumulated pathogenic factors transforming into fire.Through principal component analysis: specific symptoms of pathogenic factors encroaching on the Liver and the Lung,rib pain, chest pain,shortness of breath,red eyes red head,the main symptoms of hip pain,groin pain, dizziness ringing in the ears,tongue blood ecchymosis,the secondary symptoms of upset irritability,Dark purple tongue,pulse and other strings.The specific syndrome of obstruction in joints attacked by pathogenic factors:knee pain,ankle pain,heel pain,mainly light red tongue symptoms,secondary symptoms such as upper extremity joint pain.syndrome of deficiency in kidney and Du Channel with cold -specific symptoms of chills warm hi,four at the end of non-temperature,urine-money long,bleak tongue,thin white coating,the main symptoms of lumbosacral pain,neck pain,weakness in the waist and knee,hump-back deformity secondary symptoms for dilute stool soft,weak pulse foot,back pain,aggravated at night,pulse Shen,hip deep in pain,man or woman scrotum leucorrhea cold cold slippery moss,such as greasy,syndromes of impairment of kidney by damp-heat -specific permit for the mouth was bitter and sticky,greasy yellow coating,the main symptoms of hand,foot and heart fever,symptoms of secondary side of a sharp red tongue,syndrome of accumulated pathogenic factors transforming into fire of the specific symptoms of joint swelling heat pain, the main symptoms,fever,bad cold-hi heat,dry stool,urine short,thin yellow tongue coating, pulse a few,minor symptoms of moming stiffness,palpitations,sublingual Choroid blood Qu, greasy and yellow and white with moss,and other small pulses.Conclusions:This study of 2218 cases of clinical data of AS patients with a more comprehensive analysis,to improve the understanding of the clinical characteristics of the disease,suggesting that attention should be paid to younger age at onset of AS trend;attention to male patients with juvenile onset AS ratio;attention to female patients with AS HLA-B27 negative ratio;attention to the first part of the distribution of AS characteristics;importance of AS peripheral joint disease;importance of AS and the involved hip bone mass reduction in the incidence of osteoporosis and so on.Differentiation of clinical instructors of the five types of AS activity Syndromes Logistic regression analysis to establish a prediction model differentiation tests,clinical evidence syndrome of obstruction in joints attacked by pathogenic factors correct prediction rate of 83.2 percent,and the remaining four card-based clinical prediction accuracy are large at 90%, suggesting that differentiation prediction model suitable for clinical use to improve the clinical feasibility.This study used cluster analysis of the TCM Syndrome AS objective elements of the induction,classification,to avoid the differentiation of the subjective judgments of the defects, cluster analysis of the results of clinical syndromes and the teacher basically consistent with classification on clinical syndromes mentor Category have high scientific,objective,realistic and worthy of further promotion.The use of principal component of the load on the AS number of TCM Syndrome for quantitative assessment,the TCM Syndrome symptoms in a more simplified and quantified for the differentiation of clinical classification. Cluster analysis combined with principal component analysis to achieve a clinical syndrome of AS elements into traditional Chinese medicine and the purpose of extraction,it is worth further study and application.更多还原