The relationship between primary biliary cholangitis and Sjögren's syndrome / 临床肝胆病杂志

Both primary biliary cholangitis and Sjögren's syndrome belong to chronic autoimmune epithelitis, and they often occur at the same time. This article reviews the general features, clinical manifestations, serological features, pathogenesis, treatment regimens, and common features of primary biliary cholangitis and Sjögren's syndrome and explores the common pathogenesis of the two diseases, so as to provide ideas for developing new therapies and management strategies for patients.

The relationship between primary biliary cholangitis and Sjögren's syndrome / 临床肝胆病杂志

Both primary biliary cholangitis and Sjögren's syndrome belong to chronic autoimmune epithelitis, and they often occur at the same time. This article reviews the general features, clinical manifestations, serological features, pathogenesis, treatment regimens, and common features of primary biliary cholangitis and Sjögren's syndrome and explores the common pathogenesis of the two diseases, so as to provide ideas for developing new therapies and management strategies for patients.

Related factors of hyperuricemia in IgA nephropathy patients / 中华肾脏病杂志

Objective@#To investigate the influencing factors of hyperuricemia in patients with IgA nephropathy (IgAN).@*Methods@#A retrospective study was performed in patients with renal biopsy diagnosed as IgAN in the Department of Nephrology, Provincial Hospital of Anhui Medical University from January 2016 to October 2018. According to the blood uric acid level, they were divided into two groups: patients with hyperuricemia and patients without hyperuricemia. The general clinical indicators and renal pathological data were compared between the two groups. Logistic regression model was used to analyze the influencing factors of hyperuricemia in IgAN patients.@*Results@#A total of 125 IgAN patients with age of (35.70±11.16) years old were enrolled, including 63 males and 62 females. The morbidity of hyperuricemia was 44.0%(55/125). Compared with the normal blood uric acid group, the blood urea nitrogen, serum creatinine and the proportion of chronic kidney disease (CKD) stage 3-5, small arterial wall thickening, fibrous crescents/globules, renal interstitial fibrosis, renal tubular atrophy, glomerular sclerosis and inflammatory cell infiltration in the hyperuric acid group were higher, while the level of estimated glomerular filtration rate (eGFR) was lower. And the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the level of serum creatinine was an independent related factor of hyperuricemia in IgAN patients (OR=1.034, 95%CI 1.005-1.064, P=0.021).@*Conclusions@#IgAN patients with hyperuricemia presented more severe glomerular, tubular and interstitial lesions, and the level of serum creatinine is an independent related factor of hyperuricemia in IgAN patients. High uric acid level may have an important influence on the progression of IgAN, so good control of serum uric acid may improve the prognosis of patients with IgAN.

The clinical characteristics of 346 patients with IgG4-related disease / 中华内科杂志

Objective To analyze the clinical characteristics of IgG4-related disease (IgG4-RD)so as to improve the understanding of IgG4-RD in China.Methods IgG4-RD patients were recruited from Peking Union Medical College Hospital between January 2011 and January 2016.All patients were followedup for more than 6 months.The demographic characteristics,symptoms,organ involvements,laboratory examinations and treatment efficacy were evaluated and analyzed.Results A total of 346 patients were finally enrolled,including 230 males (66.5％) and 116 females (33.5％).The mean age of disease onset was (53.8 ± 14.2) years old.The mostly common involved organs were lymph nodes (56.4％) and submandibular glands (52.6％).Other affected organs and manifestations included:swelling of the lacrimal glands (46.5％),autoimmune pancreatitis (38.4％),pulmonary involvement (28.0％),sclerosing cholangitis (25.4％),naso-sinusitis (23.4％),parotid gland swelling (21.7％),retroperitoneal fibrosis (19.9％),large arteries involvement (9.5％),kidney involvement (obstructive nephropathy caused by retroperitoneal fibrosis was excluded) (6.9％),skin lesions (6.4％).Rare features consisted of thyroid glands,pituitary glands,gastrointestinal tract,pachymeningitis,pericardium,sclerosing mediastinitis and orchitis.The majority of patients had multi-organ involvement,such as 74.3％ patients with 3 and more,18.2％ and 7.5％ patients with 2 and single organ involvement respectively.The average IgG4-RD responder index (IgG4-RD RI) was 13.21 ±5.70.History of allergy was found in 172 (49.7％) patients.As to the laboratory tests,elevated serum IgG4 levels were confirmed in 285 (94.1％) patients,which was positively correlated with IgG4-RD RI.There were 33.5％ patients receiving monotherapy of glucocorticoid,52.6％ treated with glucocorticoids combined with immunosuppressive agents,4.9％ patients with immunosuppressant only,and 9.0％ patients with mild disease not receiving medication.The majority (336,97.1％) patients improved the above regimens.Conclusion IgG4-RD is a systemic fibro-inflammatory disease with multiple organ involvement.The mostly common involved organs include lymph node,submandibular glands,and pancreas.Glucocorticoids and immunosuppressive agents were effective for IgG4-RD.

Myasthenia gravis complicated with polymyositis: a report of three cases and literature review / 中华全科医师杂志

Three female patients admitted with elevated creatine kinase,impaired muscle on electromyogram,and positive repetitive nerve stimulation and neostigmine tests were diagnosed as polymyositis (PM) with myasthenia gravis (MG).Twenty five more cases were retrieved by literature search,and the clinical data of total 28 cases were analyzed.There were 10 males and 18 females with an average age of 56 years.The clinical manifestations include dyspnea(43％),dysphagia(43％),ptosis (43％),dysarthria(29％),diplopia(18％),cough after drinking(14％),myalgia(11％).Thirteen out of 26 cases (50％) had positive results in repetitive nerve stimulation (RNS) and 10/11 showed positive reaction in neostigmine test.Serum positive anti-acetylcholine receptor was detected in 21 out 23 patients (91％).

Clinical analysis of Takayasu's arteritis with cardiomyopathy / 中华全科医师杂志

The clinical data of 13 patients diagnosed as Takayasu's arteritis with cardiomyopathy in Peking Union Hospital were reviewed.Echocardiography showed cardiomegaly (left chambers mainly),diffuse weakened myocardial wall movement and reduced left ventricular ejection fraction.Dilated cardiomyopathy was diagnosed in two patients.Glucocorticoid and cyclophosphamide were the essential medication for treatment.One patient died,1 patient was aggravated and the disease condition in remaining 11 patients was stable or improved.Takayasu's arteritis with cardiomyopathy is a rare disease and it attacks younger people.It is difficult to identify at onset,and the disease deteriorates rapidly.Echocardiography should be performed earlier to evaluate the heart function for early diagnosis and treatment.Administration of large dose of glucocorticoid and cyclophosphamide at early stage may improve the prognosis.

Clinical features of primary Sj(o)gren's syndrome with pulmonary hypertension / 中华全科医师杂志

The clinical data were collected from medical record of 749 patients admitted into Peking Union Medical College Hospital from January 2008 to March 2013.They were diagnosed with primary Sj(o)gren's syndrome (PSS) at discharge.Clinical manifestations,laboratory results and outcomes were compared between PSS patients with pulmonary hypertension (PSS-PH) and those without (PSS-non PH).PSS-PH group had higher proportions of Renault phenomenon (36.8％ vs.20.0％,P =0.05),pericardial effusion (55.3％ vs.0.0％,P＜0.01),leukocytopenia (42.1％ vs.30.0％,P =0.03),elevated IgG level [(28.8 ±11.2) vs.(21.5 ±10.0) g/L,P=0.01] and hypothyroidism(34.2％ vs.12.5％,P=0.05) with significant significance.The PSS patients had leukocytopenia low thyroid function,rising IgG and pericardial effusion with pulmonary hypertension.

Clinical study on IgG4-related autoimmune pancreatitis / 中华风湿病学杂志

Objective To investigate the clinical features of IgG4-related autoimmune pancreatitis (IgG4-related AIP).Methods A prospective cohort study on IgG4 related disease (IgG4-RD) was carried out in Peking Union Medical College Hospital during December 2010 to June 2012,a total of 50 patients were recruited,including 14 IgG4-related AIP patients.The clinical manifestations,laboratory tests results,radiographic findings,histopatholo-gical lesions and response to treatment were analyzed.Results Fourteen AIP patients accounted for 28％ of IgG4-RD,of whom 9 cases were male,5 females,with the mean age of (55±10) (range 41-71) years.Painless obstructive jaundice was the major manifestation of AIP.All patients had extra-pancreatic organ involvement,including salivary glands enlargement (10 cases),lymph nodes swollen (7 cases),and bile duct tree (6 cases),lung (6 cases),kidney (2 cases),lacriminal gland (2 cases),retroperitoneal tissue (1 case),mesentery (1 case),and prostate (1 case) involvement.Serum levels of IgG4 subclass in all patients were significantly increased,with mean concentration of (11 ±10) (range 1.4-35.2) g/L.Radiographic findings showed diffuse (13 cases) or focal (1 case) pancreatic enlargement with irregular narrowing of the pancreatic duct (4 cases).Histopathological examinations were performed in 12 patients,which revealed massive infiltration with lymphocytes and IgG4 positive plasma cells with remarkable tissue fibrosis.Response to glucocorticosteroid or combined steroid and immunosuppressants were good.Conclusion IgG4-related AIP is a subtype of chronic pancreatitis,which is characterized by specific clinical spectrum,serological markers,radiographic and histopathological features.Glucocorticosteroid is the first choice,which can significantly improve the clinical and imaging abnormalities.

Causes of death of systemic lupus erythematosus patients in the past twenty-five years / 中华风湿病学杂志

ObjectiveTo investigate the changes of major causes of death of patients with systemic lupus erythematosus(SLE).MethodsDeath cases with SLE from January 1986 to May 2011 in Peking Union Medical College Hospital were retrospectively analyzed.ResultsOut of 3554 patients with SLE,252 patients died,including 223 women and 29 men.The mortality rate was 7.2％ among female and 6.2％ among male,the overall mortality rate was 7.1％.The mortality rate in SLE patients had dropped steadily in the past 25 years,but there was a mild increase of mortality in 2006-2011 compared with that in 2001-2005 (5.7％vs 5.3％ ).In addition to infection,neuropsychiatric lupus and lupus nephritis had become the most common causes of death in SLE patients during the past 25 years.Furthermore,diffuse alveolar hemorrhage,severe pulmonary hypertension,coronary heart disease,thrombocytopenia,interstitial lung disease,lupus pneumonia,gastrointestinal hemorrhage, intestinal obstruction and multiple organ failure were the common causes of death,accounting for 4.4％,4.4％,3.2％,2.8％,2.4％,2.0％,2.0％,1.2％ and 1.2％ of all the death cases respectively.From 1986 to 2005,infection,neuropsychiatric lupus and lupus nephritis were the most common causes of death in patients with SLE,whereas the cases dying from lupus nephritis had decreased obviously and severe pulmonary hypertension had become the third most frequent causes of death during the past 5years.From 1986 to 1990,lupus nephritis,infection and neuropsychiatric lupus accounted for 31.4％,25.7％and 25.7％ of death cases respectively.From 1991 to 1995,lupus nephritis,infection and neuropsychiatric lupus accounted for 27.6％,24.1％ and 24.1％ respectively.From 1996 to 2000,infection,neuropsychiatric lupus and lupus nephritis took up 31.6％,21.1％ and 15.8％ respectively.From 2001 to 2005,infection,neuropsychiatric lupus and lupus nephritis took up 34.9％,20.6％ and 7.9％ respectively.From 2006 to 2011,infection, neuropsychiatric lupus and pulmonary hypertension accounted for 60.3％, 11.8％ and 7.4％ respectively.The mortality in the first year was the highest in the whole disease course,accounting for 32.5％ of patients.Deaths caused by neuropsychiatric lupus and infection happened most frequently during the first year,accounting for 41.9％ and 32.9％,whereas deaths caused by lupus nephritis occurred most frequently 10 years later,accounting for 32.3％.Age and gender had significant association with the major causes of death.The male patients took up 50.0％ of the total patients dying from coronary heart disease,in which 75.0％ of patients were older than 50 years.ConclusionInfection,neuropsychiatric lupus and lupus nephritis are the three most common causes of death in SLE patients fron 1986 to 2005.Severe pulmonary hypertension has become the third most frequent causes of death during the past 5 years instead of lupus nephritis.Severe infection has increased significantly and has been the leading cause of death in SLE patients in recent 5 years.

Analysis of locations and pathogens of systemic lupus erythematosus cases died from infection / 中华风湿病学杂志

Objective To investigate the location and the pathogens of systemic lupus erythematosus (SLE) patients who died from infection.Methods Dead cases of hospitalized SLE patients in Peking Union Medical Hospital from January 1986 to May 2011were retrospectively analyzed.Results Severe infection was an important cause of mortality in patients with SLE.There were 252 dead cases of SLE in total from 1986 to 2011,in which 97 cases died from severe infection.The proportion of patients died from infection was gradually increased during the past 26 years,which was 25.7％,24.1％,31.6％,34.9％ and 60.3％ in 1986-1990,1991-1995,1996-2000,2001-2005 and 2006-2011respectively.Lung was the most common site of infec-t ion,accounting for 65％ of all dead cases.Among the 31cases with identified microorganism,14 patients had single microorganism infection and 17 patients had mixed infections.In the single microorganism infection patients,fungal infection contributed to the cause of death in 9 out of 14 (64％) patients,of which 4,2,1,1,and 1 cases were infected with Pneumocystis carinii, Aspergillus fumigates,Fusarium,Candida tropicalis and Cryptococcus respectively.There were 3 cases of bacteria infection,including 2 cases with Methicillinresistant staphylococcus,aureus and 1case with Klebsiella pneumoniae infection.Two patients died from pulmonary tuberculosis.In 17 patients with mixed infection cases, 14 deaths were caused by bacteria infection,including Acinetobacter baumannii, Eschefichia coli, Enterococcus, Klebsiella pneumoniae,Pseudomonas aeruginosa and Enterobacter cloacae.Eleven patients died from mixed fungus infection,including 6 cases of Aspergillus fumigates,3 cases of Candida tropicalis,3 cases of Pneumocystis carinii,2 cases of Aspergillus flavus,1 case of Soil Aspergillus,2 cases of Candida albicans,1 case of Candida glabrata and Candida Krusei.In addition to bacteria and fungi infection,cytomegalovirus infection occurred frequently in SLE death cases.Conclusions Severe infection has been the most frequent cause of death in SLE patients,in which lung infection is the leading cause.Pneumocystis carinii,Aspergillus fumigates,Acinetobacter baumannii and cytomegalovirus are the major pathogens that cause death in SLE patients.

The role of CXCR3 in primary biliary cirrhosis mice model / 中华风湿病学杂志

Objective To generate an primary biliary cirrhosis animal model and investigate whether CXCR3 and its ligands were involved in the pathogenesis of primary biliary cirrhosis (PBC).Methods Female C57BL/6 wild-type(WT)mice were injected with 5 mg/kg of poly I:C intraperitoneally twice a week for 24 consecutive weeks.Establishment of PBC was confirmed by liver function test,serom autoantibodies and liver biopsy.Expression of CXCR3 on lymphocytes of liver/spleen and level of CXCL10 in peripheral blood were tested by flow cytometry assay and ELISA.The t-test was used for two group data comparison.Results Anti-mitochondrial antibody was detected in the sera of all poly I:C injected wild type C57BL/6mice.Considerable numbers of inflammatory cells were detected at the portal areas 8 weeks after the initiation of poly I:C injection,which progressed up to 24 weeks.Compared the to control mice,serum level of CXCL10was increased in PBC mice.With the disease progression,CXCL10 serum level was elevated.The level of CXCL10 at 8,16 and 24 weeks in PBC model was 0.28±0.10,0.33±0.19 and 0.27±0.11,which were much higher than those of the control mice.CXCL10 serum level of control mice was 0.07±0.03.0.08±0.05,0.10±0.04 respectively.Compared to control model,the proportion of CXCR3+ positive cells was inereased in the intrahepatic infiltrates of PBC model,mostly on CD8+ T cells.Moreover,the expression of CXCR3 was decreased in CD3+and CD8+splenocytes from PBC model compared with control model.Conclusion CXCR3and CXCL1O may attract T cells to the liver of PBC mice mode in the process of PBC development

The role of CXCR3 knockout in alleviating the primary biliary cirrhosis in mice / 中华风湿病学杂志

Objective To generate an autoimmune cholangitis animal model and investigate whether CXCR3 and its ligand were involved in the pathogenesis of primary biliary cirrhosis (PBC). Methods Female C57BL/6 wild-type (WT) mice and CXCR3 knockout (CXCR3-/-) mice were injected with 5 mg/kg of poly I:C intra-peritoneally twice a week for 24 consecutive weeks. Liver specimens were collected to evaluate the degree of cell infiltration. AMA was assayed by ELISA. Differences in pathology were compared between CXCR3-/- mice and wild-type. Student's test was used to assess the differences. Results Anti-mitochon-drial antibody (AMA) and alkaline phosphatase (ALP) level were elevated significantly in the sera of all poly Ⅰ:C injected mice compared with control mice. AMA titers in serum were increased in the poly I:C injected WT mice compared with that of the control mice at week 8, 16, and 24 respectively (0.70±0.41 vs 0.17±0.04,0.48±0.35 vs 0.19±0.07, 0.69±0.44 w 0.20±0.06, P＜0.01). There was no significant difference between AMA titers in the serum of WT PBC mice and CXCR3-/- PBC mice (0.70±0.41 vs 0.56±0.25, 0.48±0.35 vs 0.46±0.35, 0.69±0.44 vs 0.85±0.34). Serum alkaline phosphatase (ALP) levels were raised among the poly I:Cinjected WT mice compared with WT controls (115±33) vs (65±7) U/ml; (119±32) vs (70±9) U/ml; (133±52) vs (77±10) U/ml. The serum ALP levels in CXCR3-/- PBC mice were (106±29), (112±29)and (122±60) U/ml at week 8, 16 and 24 respectively. There was no significant difference in ALP level between WT and CXCR3-/- mice PBC model. Considerable numbers of infiltrating cells were detected at the portal areas 8weeks after poly I:C injection, which progressed up to 24 weeks. At week 24, the interlobular bile ducts were lost and bile-plug were evident. Compared to WT mice model, this results revealed that CXCR3-/- mice, had fewer foci of inflammation and significant reduction in total inflammatory cells in their livers than those of the WT mice at 8, 16 and 24 weeks after injection of poly I:C. At week 24, there were no cholestasis orgranulomas in CXCR3-/- mice of PBC models. Compared to the control model, CXCL10 serum level was increased in PBC model. With the disease progression, CXCL10 serum level was elevated gradually. In comparison with wild mice, CXCR3-/- mice model had a higher serum level of CXCL10. At week 24, there was significant difference of CXCL10 serum level between wild-type mice and CXCR3-/- mice model. Conclusion In conclusion, these findings indicate that, CXCR3-/- mice might have a delayed onset and ultimately could not recruit sufficient effector cells to the liver for inflammation development.

Clinical observation of the therapeutic responses of primary biliary cirrhosis / 中华风湿病学杂志

Objective The aims of this study were to compare the clinical and laboratory responses to ursodeoxycholic acid (UDCA) monotherapy with the combination therapy of UDCA plus prednisolone/azathioprine in primary biliary cirrhosis(PBC),and to investigate the risk factors affecting the therapeutic responses.Methods Eighty-two patients with untreated PBC were divided randomly into three groups.Group U (28 patients) received UDCA alone,group UP(27 patients) received UDCA and pr ednisolone,while group UA (27 patients ) received UDCA and azathioprine.The clinical and laboratory data were recorded after treated for 3,6 and 12 months.Repeated measures ANOVA and COX regression model were used for statistical analysis.Results Fatigue and pruritus were improved only in group UP(P=0.015 and P=0.037 respectively).Alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),gamma-glutamyl transferase (GGT),total bilirubin (TBIL),direct bilirubin (DBIL) and IgM in the 3 groups were decreased (P＜0.05),while there was no statistical significant difference between the three groups (P＞0.05).The patients with disease progression had higher Mayo risk score (MRS) (P=0.018) and prolonged prothrombin time (PT)(P=0.042).In group UP,side-effect associated with glucocorticosteroids occurred in eight patients while there was no side-effect in group U.High baseline levels of ALP、GGT and CHO were risk factors for biochemical remission(P=0.015).The increase of DBIL,TBIL,total bile acid(TBA) and PT did not contribute to the prediction of biochemical remission ( P=0.075 ).Conclusion There are no differences among the three groups in the improvement of hepatic biochemical data and IgM.The combination therapy of UDCA with prednisolone could relieve fatigue and itching.The disease of patients with higher Mayo risk score and prolonged PT tend to progress.High baseline levels of ALP,GGT and CHO are risk factors for biochemical remission.High baseline levels of TBIL,DBIL,TBA and PT could not predict biochemical remission.The incidence of adverse effect is lowest when treated with UDCA alone.

Clinical features of primary biliary cirrhosis associated with systemic sclerosis / 中华风湿病学杂志

Objective To assess the clinical features of primary biliary cirrhosis(PBC)associated with systemic sclerosis(SSc)in order to facilitate recognition of this overlap syndrome(SSc-PBC). Methods The clinical data of 9 patients with SSc-PBC in Peking Union Medical College Hospital were retrospectively studied with literature review. Results ① Nine patients including 8 female were at a mean age of(54±8)years. Sevene patients initially presented with SSc and developed PBC over(4.3±2.3)years. ② Eight patients were diagnosed limited cutaneous SSc(leSSc), which included 7 patients with CREST syndrome. The most frequent manifestations were Raynaud's phenomenon(8/9)and esophageal dysfunction(8/9). Four patients with PBC manifested subclinically, but laboratory results revealed increased ALP/GGT in most patients(8/9).Two patients received liver biopsies, which confirmed the diagnosis of PBC. ③ Antinuclear antibodies(ANA)and anti-mitochondrial antibody(AMA)were detected in all the patients, among them, 8 with positive anticentromere antibody(ACA)and 8 with positive AMA-M2. ④ UDCA and glucocorticosteroid might help early stage patients with SSc-PBC, but lack efficacy in patients complicated with interstitial lung disease, pulmonary hypertension or cirrhosis. Conclusion PBC might be overlapped with SSc, especially lcSSc(CREST syndrome). Screening of autoantibodies, such as ACA, AMA and AMA-M2, could help rheumatologists early recognition of SSc-PBC and improve the prognosis of this overlap syndrome by early intervention.

Analysis of anticardiolipin antibody fluctuation and clinical manifestations in systemic lupus erythema-tosus patients / 中华风湿病学杂志

Objective To investigate the association of fluctuation of anticardiolipin antibody (ACA) levels and clinical manifestations in patients with systemic lupus erythematosus (SLE). Methods Anticar-diolipin antibodies were measured sequentially by commercial enzyme-linked immunosorbent assay (ELISA) in 85 SLE patients. Patients were classified into two groups: group A was persistently positive for ACA, group B was transiently positive for ACA, and the clinical features of the two groups were compared. Results There were 37 patients (44%) in group A, and 48 (57%) patients in group B. 41% patients had occurred thromboeytopenia in group A, 19% patients in group B, the difference was significant (P<0.05); platelet accounts were (24±6)×109/L in group A,and (46±10)×109/L in group B, the difference was significant (P< 0.05), too. 11% patients experienced thrombosis in group A, and none in group B, the difference was significant (P<0.05). 19% in group A and 4% in group B had occurred valvular diseases, the difference was significant (P<0.05.). The prevalence of lupus anticoagulant was 32% in group A, 13% in group B and the difference was significant (P<0.05). There was no significant difference between the two groups in Raynaud's phenomenon, pulmonary hypertension, and lupus nephritis (P0.05). Conclusion Fluctuations of anticardio-lipin antibodies are asso-ciated with thrombosis, thrombocytopenia vascular disease and lupus anticoagulant however, there is no lack of association with other clinical manifestations in SLE patients.