A Retrospective Study On The Clinical Characteristics Of Sjogren’s Syndrome Patients With Liver-Kidney Yin Deficiency And The Rule Of Traditional Chinese Medicine Use And Discussion On The Treatment Of Sjogren’s Syndrome From The Liver.

Objective:Individualized diagnosis and treatment based on syndrome differentiation of TCM have unique advantages in alleviating the symptoms of dryness and improving the quality of life.Through collecting the clinical characteristics of liver-kidney yin deficiency syndrome,the most common syndromes of Sjogren’s syndrome in the clinic,and summarizing the characteristics of Chinese medicinal,we explored the relationship between the pathogenesis of Sjogren’s syndrome and liver visceral manifestations(including qi movement,yin-blood as well as consciousness),in order to add ideas to increase the clinical basis for the treatment of Sjogren’s syndrome based on liver theory.Methods:A retrospective study was conducted to collect the clinical data,main symptoms,use of traditional Chinese medicines,serological examination,labial gland and gastrointestinal pathology as well as a parotid gland,cervical lymph node,thyroid,breast ultrasound,and ESSPRI subjective score(dry,fatigue,pain VAS score)of female patients with Sjogren’s syndrome from 2019 to 2020 in the outpatient and inpatient department of Jiangsu Provincial Hospital of TCM,who were aged 18 to 70 years old and diagnosed as liver-kidney yin deficiency in TCM.Based on the above data,the relationship between Sjogren’s syndrome and TCM liver visceral manifestation was discussed.Statistical software packages of SPSS 22.20,Prism8.0 and R version 4.0.4 were used for data analysis.The measurement data were subjected to mean standard deviation;the enumeration data were subjected to chi-square test;the independent samples were subjected to t-test;the non-normal distribution was analyzed and compared by rank-sum test.Results1.Clinical data and main symptomsThis study included 384 female patients with Sjogren’s syndrome of liver-kidney yin deficiency in the outpatient and inpatient departments of Rheumatology and Immunology,Jiangsu Provincial Hospital of Traditional Chinese Medicine,aged between 22 and 70 years old,with an average age of 50.45 10.29 years old.Among them,142 cases from the inpatient department were detailed,with an average age of 51.53±9.78 years,a course of 5.16±4.80 years,and an onset age of about 46 years.The symptoms of 142 patients were dry mouth,dry eyesjoint pain,fatigue or weakness,insomnia,multiple dental caries or rampant teeth,cough,ulceration,dry stool or constipation,and soreness of the waist and knees.142 patients scored an average of 11.35 3.74 points in the subjective score of ESSPRI,which was artificially divided into three groups:mild dryness(27 cases,19.01%),dryness as the main manifestation group(66 cases,46.48%),and pain as the main manifestation group(49 cases,34.51%),with an average of 7 points,12 points,and 13 points respectively.most of which were medium subjective scores.2.Serological examinationIn this study,patients’ WBC decreased by 42%,globulin increased by 52.02%in liver and kidney function,IgG increased by 58.05%,RF increased by 54.35%,CRP increased by 6.60%,and ESR increased by 32.25%.Among them,the serological correlation analysis of 139 cases from the inpatient department showed that RF was positively correlated with IgG,IgM,TP,GLOB,ESR,and other globulin-related indicators,which may affect blood viscosity.The total ANA positive rate was 91.89%,with the highest ANA 1:320 rates of 36.47%and the maximum number of nuclear granules-cytoplasm karyotypes of 58.70%.The 11 positive rates of ANA antibody spectrum mainly include the following four kinds:the positive rate of anti-SSA antibody is 69.04%,the positive rate of anti-Ro-52 antibody is 64.93%,the positive rate of anti-SSB antibody is 30.14%,and the positive rate of anti-centromere antibody is 11.78%.3.Pathological examinationA pathological report of lip gland biopsy was presented in 72 cases,with a positive rate of 88.89%.Gastric and intestinal pathology was reported in 67 and 47 cases,respectively.The percentages of atrophic gastritis and intestinal metaplasia detected by gastric histopathology were 35.82%and 43%,respectively,higher than the national epidemiological survey level.The percentages of the gastric and intestinal proliferation of lymphoid follicles or lymphocyte aggregation were 22.39%and 46.28%,respectively,and the proliferation of lymphoid follicles or lymphocyte aggregation in the large intestinal tissue was significantly increased(P<0.01).4.Ultrasonic examinationThe result shows a high incidence of glandular nodules or enlargement.A total of 60 cases of parotid gland ultrasonic pathology were collected,and the report content was that the sum of diffuse-like lesions,non-uniform echo,and positive rate of parotid gland enlargement was 71.67%.There were 89 cases of thyroid ultrasound,including 28.09%of diffuse thyroid changes and 62.90%of nodular thyroid lesions.The total positive rate was 73.03%,which was higher than the level of epidemiological investigation of thyroid nodules reported in the literature from multiple regions in China.Cervical ultrasound was performed in 20 cases,and lymphadenopathy was reported as 80%of the total cases.A total of 67 cases of breast ultrasound were collected,and the sum of the proliferation rates of hyperplasia of mammary glands,nodules,cystic nodules,incomplete degeneration,and catheter dilatation was reported to be 92.68%,the incidence rate of which was significantly higher than 78.13%of female patients with the non-Sjogren’s syndrome in our hospital during the same period(P<0.01).5.Frequency of use of Chinese medicinal303 prescriptions(visits)involved 273 Chinese medicinal with a frequency of 4,367,with 27 medicines in the most prescription and at least three medicines in the least,with an average value of 14.39±3.89 and the median value of 15.The top 30 Chinese medicinal accounted for 54.82%of the total medication frequency,with Ophiopogon Japonicus 4.69%,Glycyrrhizae Radix 4.14%,and Rehmanniae Radix 3.89%being the most widely used ones.Distribution of efficacy:The top five Chinese medicinal accounted for three-quarters of the total number,namely,35.79%of deficiency tonics drugs(20.47%of yin tonics drugs),21.39%of heat-clearing drugs(8.29%of blood-cooling drugs),7.53%of blood-activating and stasis-resolving drugs,5.11%of qi-regulating drugs and 4.76%of exterior-relieving drugs.Among them,the blood-activating and blood-nourishing herbs accounted for 21.45%and 91.72%of the total usage frequencies of all the Chinese medicinal,including raw Radix Rehmanniae,Radix Paeoniae Alba,Radix Salviae Miltiorrhizae,and Radix Angelicae Sinensis.The four qi are mainly cold and slight cold(49.46%),supplemented by warm(24.47%)and mild(22.75%).In five flavors,the main ones were sweet(42.87%),bitter(30.96%)and pungent(17.62%).Among them,the most commonly used ones for pungent were pungent and warm(62.15%),which were mainly distributed in qi-regulating herbs,exterior-relieving herbs,heat-clearing herbs,deficiency-reinforcing herbs,blood-activating,and stasis-resolving herbs,phlegm-resolving,cough-relieving,and asthma-relieving herbs,such as Pericarpium Citri Reticulate,Radix Bupleuri,Cortex Moutan,and Radix Asteris.For meridian tropism,lung meridian(19.74%)and liver meridian(16.90%)were the most abundant,followed by stomach,spleen,heart,and kidney meridians,and the total six meridians exceeded 90%of the usage frequency.Chinese medicinal is generally sweet,cold,and moist,which mainly enters the lung and liver meridians,nourishes yin,and moistens dryness,supplemented by pungent,bitter,and warm herbs,as well as the ones that move qi,nourish the blood,and activate blood.6.Cluster analysis of Chinese medicinalThe first 30 Chinese medicinal with a higher utilization rate could be divided into three categories:the first one was Radix Ophiopogonis,Herba dendrobium,Radix Glehniae,Radix Adenophorae,Radix Rehmanniae,and Radix Glycyrrhizae,which could be viewed as modified Shashen Maidong Decoction.The second type is composed of Pericarpium Citri Reticulatae,Radix Salviae Miltiorrhizae,Radix Scrophulariae,and Herba Bidentis Bipinnatae,which are effective for regulating qi,clearing heat,activating blood,and promoting salivation.For the third category,Radix Bupleuri,Radix Paeoniae Alba,Radix Paeoniae Rubra,Radix Angelicae Sinensis,Poria,Rhizoma Atractylodis Macrocephalae,Rhizoma Dioscoreae,Fructus Corni,Cortex Moutan,Fructus Lycii,Flos Chrysanthemi,Radix Scutellariae,and Radix Asteris can be regarded as the modified of Xiaoyaosan and Qiju Dihuang Pill,or Zishui Qinggan Decoction.ConclusionThe clinical features of Sjogren’s syndrome of deficiency of liver-kidney yin are based on yin deficiency with qi stagnation and blood stasis.It is reflected in the following three aspects:First,the affected parts of the main symptoms are mostly distributed along the liver meridian,and due to liver qi stagnation,anxiety and depression occur frequently.Second,serological examination,pathological examination of gastrointestinal tissues,and ultrasound examination of the parotid gland,thyroid,and breast showed mostly liver stagnation,qi stagnation,and blood stasis.Third,the use of Chinese medicinal is based on nourishing yin,which combines soothing liver and moving qi,nourishing and activating blood.Clinical clustering analysis showed that Shashen Maidong Decoction combined with Zishui Qinggan Decoction was mainly used in the prescriptions for the treatment of dryness.In combination with the above three aspects and theoretical analysis,the pathogenesis of Sjogren’s syndrome of liver-kidney yin deficiency is closely related to liver visceral manifestations.The theory of "predominant dryness causing withering" can be developed from qi stagnation and blood stasis,which means that based on liver and kidney yin deficiency,qi stagnation and blood stasis,as well as collateral stagnation and fluid impairment,are the basic pathogenesis of the disease.On the basis of nourishing yin and kidney,attention should be paid to soothing liver,nourishing liver,and even clearing the liver,as well as the application of pungent and scattered herbs and blood-nourishing and activating herbs,so as to achieve the purposes of nourishing liver and kidney,moving qi and activating blood,and dredging collaterals.