Clinical features of patients with connective tissue disease combined with sarcoidosis / 中华风湿病学杂志

Objective:To investigate the clinical features of patients with coexisting connective tissue disease (CTD) and sarcoisosis and to avoid misdiagnosis and mistreatment.Methods:To analyze the clinical manifestations, laboratory data, imaging and pathological features of patients with CTD combined with sarcoidosis in Peking Union Medical College Hospital from January 1985 to December 2021.Results:There were 17 patients with CTD(including 10 SS, 2 DM, 2 PBC, 1 SLE, 1 RA and 1 UCTD), combined with sarcoidosis, with a mean age of (55±10) years old and the ratio of male-to-female was 1:16. Eight patients were diagnosed as CTD before sarcoidosis, while 3 patients after sarcoidosis. The other 6 patients were diagnosed with the two diseases almost simultaneously. Lymphadenopathy(12/17), pulmonary nodules (8/17), subcutaneous nodules (4/17), rash (4/17) and blurred vision (1/17) were the main manifestations of patients with the onset of nodular disease. Nine patients were treated based on the presentation of sardoisis and 5 patients for CTD; 3 patients were treated for both diseases at the same time. All 17 patients discharged with improvement after treatment.Conclusion:When sarcoidosis do coexists with CTD, occult CTD might occur. It is important to investigate specific manifestations including pathological features of sarcoidosis and differentiate it from CTD.

Clinical characteristics of patients with rheumatic diseases and abnormal liver function / 中华内科杂志

Objective:To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities.Methods:Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups.Results:A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)].Conclusions:The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients′ liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

Clinical characteristics of 37 antiphospholipid syndrome patients complicated by autoimmune hemolytic anemia / 中华内科杂志

Objective:We sought to investigate the clinical characteristics and risk factors of antiphospholipid syndrome (APS) complicated by autoimmune hemolytic anemia (AIHA).Methods:Retrospective anaysis.Three hundred fifteen consecutive patients with APS were enrolled at the Department of Rheumatology of Peking Union Medical College Hospital between May 2017 to May 2021, and their clinical manifestations[including initial symptoms, time interval between APS onset and diagnosis, systemic lupus erythematosus(SLE), thrombotic events, obstetric morbidity, and extra-criteria manifestations] and laboratory test results[including blood routine, antiphospholipid antibodies(aPLs), blood lipid profile, homocysteine, anti-nuclear antibody profile, immunoglobulin levels, and complement levels] were collected. Then, univariate and multivariate logistic regression analyses were performed. Clinical features and risk factors were analyzed using univariable and multivariable logistic regression analysis.Results:Among 315 APS patients, 37 cases (11.7%) were complicated by AIHA, and AIHA was the first manifestation or co-occurrence. The median time interval between APS onset and diagnosis was 12 months. The proportion of SLE in APS patients combined with AIHA was higher than that in APS patients without AIHA[62.2%(23/37) vs. 19.4%(54/278), P<0.001]. There was no significant difference in the proportions of thrombosis and pregnancy morbidity between the two groups. In terms of extra-criteria manifestations, APS patients with AIHA had a significantly ( P<0.05) greater risk of thrombocytopenia ( OR=6.19, 95% CI 2.81-13.65) and higher proportions of hypocomplementemia, a positive lupus anticoagulant (LA) result, double aPLs positivity[i.e., any two of the following antibodies were positive: LA, anticardilolipin antibody(aCL), and anti-β2 glycoprotein Ⅰ(β2GPⅠ)], and triple aPLs positivity (i.e., LA, aCL, and anti-β2GPⅠ antibodies were all positive). Multivariate logistic regression analysis showed that SLE ( OR=3.46,95% CI 1.60-7.48), thrombocytopenia ( OR=2.56,95% CI 1.15-5.67), and hypocomplementemia ( OR=4.29,95% CI 2.03-9.04) were independent risk factors for the complication of APS. In the primary APS subgroup, multivariate logistic regression analysis showed that livedo reticularis ( OR=10.51,95%CI 1.06-103.78), thrombocytopenia ( OR=3.77, 95% CI 1.23-11.57), and hypocomplementemia ( OR=5.92,95% CI 1.95-17.95) were independent risk factors for the complication of APS. Conclusions:AIHA is not rare in APS patients; moreover, it occurs more frequently in APS secondary to SLE and is more likely to present with a variety of extra-criteria manifestations. Patients with AIHA should be promptly tested for antiphospholipid antibody profiles and alerted to the possibility of thrombotic events.

Analysis of differentially expressed microRNA and protein expression profiles carried by exosomes in the plasma of patients with Takayasu′s arteritis / 中华内科杂志

Objective:To detect the microRNAs (miRNAs) and proteins carried by exosomes in the plasma of patients with newly diagnosed Takayasu′s arteritis (TAK) and analyze their possible roles in the pathogenesis of TAK.Methods:Ten patients with newly diagnosed TAK from the Department of Rheumatology and Immunology, Peking Union Medical College Hospital were selected during June-November 2020. Five healthy controls were matched with five patients by age and sex. RNA sequencing and protein mass spectrometry were used to detect miRNAs and proteins, respectively, carried by exosomes in the plasma. Differentially expressed miRNAs (DE-miRNAs) and proteins (DEPs) were screened. Thereafter, hierarchical cluster analysis, function, signal pathway, and protein domain enrichment analysis of DE-miRNAs and DEPs were performed. Finally, miRNAs and proteins related to vasculitis and autoimmunity were identified. The possible roles of the miRNAs and proteins in the pathogenesis of TAK were explored. Enumeration data were compared using Fisher′s exact probability test or Chi-square test, and a P-value<0.05 was considered significant. Results:Compared with the healthy controls, patients with TAK had 29 DE-miRNAs on their plasma exosomes. Among these DE-miRNAs, miR-101-3p, miR-122-5p, miR-143-3p, miR-185-3p, miR-192-5p, miR-194-5p, miR-19a-3p, miR-19b-3p, miR-20b-5p, miR-21-5p, miR-22-3p, miR-335-5p, miR-34a-5p, miR-3613-5p, miR-548ad-5p, miR-590-3p, and miR-7-5p were upregulated; whereas miR-1249-3p, miR-141-3p, miR-199a-5p, miR-199b-5p, miR-200a-3p, miR-200c-3p, miR-204-5p, miR-29c-5p, miR-335-3p, miR-381-3p, miR-4433b-5p, and miR-584-5p were downregulated. Finally, miR-34a-5p, miR-200c-3p, miR-143-3p, miR-22-3p, and miR-21-5p were identified. Among the 357 DEPs screened, 236 DEPs were upregulated, whereas 121 DEPs were downregulated. Finally, kallikrein B1 (KLKB1), kininogen 1 (KNG1), desmoplakin (DSP) were identified.Conclusion:MiR-34a-5p, miR-200c-3p, miR-143-3p, miR-22-3p, miR-21-5p, KLKB1, KNG1, and DSP carried by exosomes in plasma might participate in the pathogenesis of TAK by regulating vascular physiology, inflammation, autoimmunity, and other processes. They may be biomarkers and therapeutic targets of TAK.

Interpretation of the 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty / 中华骨科杂志

The American College of Rheumatology (ACR) and the American Association of Hip and Knee Surgeons (AAHKS) convened a writing group to develop a consensus report on the management of anti-rheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty in June 2022. In particular, the consensus provides significant updates on target synthetic disease modifying anti-rheumatic drugs and perioperative medication management in patients with systemic lupus erythematosus, as well as the addition of newly approved antirheumatic medications for administration. This article will interpret the consensus and provide a reference for the perioperative management of antirheumatic medications for hip and knee arthroplasty in patients with rheumatic diseases in China.

Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR) / 中华医学杂志(英文版)

BACKGROUND@#The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts.@*METHODS@#Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts.@*RESULTS@#In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0-18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59-3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01-1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01-1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs' (csDMARDs) use.@*CONCLUSIONS@#Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.

Research Progress in Antibodies Related to Autoimmune Encephalitis in Neuropsychiatric Systemic Lupus Erythematosus / 罕见病研究

Several anti-neural antibodies are associated with neuropsychiatric systemic lupus erythematosus (NPSLE) including anti-neuronal antibodies and anti-glial cell antibodies. The anti-neuronal antibodies has two types: anti-neuronal surface protein antibodies represented by anti-N-methyl-D-aspartate receptor (NMDAR) antibodies, and anti-neuronal intracellular protein antibodies. In this paper, we review and classify the anti-neural antibodies related to NPSLE.

Sex disparities in clinical characteristics of Chinese patients with systemic sclerosis / 中华内科杂志

Objective:To evaluate the differences in clinical characteristics between different genders of Chinese patients with systemic sclerosis(SSc).Methods:The data of SSc patients registered in Chinese Rheumatism Data Center between August 2008 and June 2020 were retrospectively analyzed.Results:A total of 1 844 patients with SSc were enrolled in the study. The ratio of males to females was 289 to 1 555. The onset age was (48.6±13.7) years in males and (45.5±13.1) years in females( P<0.001). Male patients represented shorter disease duration [2.0(0.0, 4.0)years vs.3.0(1.0, 7.0) years, P<0.001],higher proportion of diffuse cutaneous SSc (dcSSc) [63.0% (182/289)vs.44.2%(688/1 555), P<0.001]. Although more man patients experienced smoking [47.4%(137/289) vs. 1.7%(27/1 555), P<0.001] and exposure to harmful environments [7.6%(22/289) vs. 2.1%(33/1 555), P<0.001], there was no statistically significant difference in interstitial lung disease between male and female patients [69.3%(181/261) vs. 74.5%(1 085/1 457), P=0.084].Otherwise, Raynaud′s phenomenon [87.7% (1 364/1 555) vs.75.4%(218/289), P<0.001], arthritis [11.1%(173/1 555) vs.6.9%(20/289), P=0.032], gastroesophageal reflux disease [22.0%(342/ 1 555) vs.13.1%(38/289), P=0.001], and leucopoenia [10.7(161/1 511)% vs. 6.1%(17/279), P=0.019] were more common in female patients, but finger ulcer was less common [22.5%(350/1 555) vs. 30.4%(88/289), P=0.004]. Antinuclear antibody(ANA) positivity rate [85.6%(1 310/1 531) vs. 78.6%(221/281), P=0.003], anti-RNP antibody positivity rate [23.1%(342/1 479) vs.14.0%(38/271), P=0.001], anti-SSA antibody positivity rate [28.2%(419/1 487) vs.13.9%(38/274), P<0.001] were higher in female patients. Physician′s global assessment(PGA) scores [1.4 (1.0, 2.0) vs. 1.0 (0.3, 1.6), P<0.001] and modified Rodnan Skin Score(mRSS) [18.0 (9.5, 28.0) vs. 14.0 (5.0, 28.0), P=0.003] were higher in males. Conclusion:Even though male SSc patients account for a small proportion, more extensive skin involvement, finger ulcers and higher PGA are manifested in males. Physicians need pay attention to these clinical disparities between different genders in SSc.

Risk factors of ankylosing spondylitis with premature coronary heart disease / 中华风湿病学杂志

Objective:To analyze the risk factors of patients with ankylosing spondylitis (AS) combined with premature coronary atherosclerotic heart disease (PCAD).Methods:A total of 74 patients with AS and coronary atherosclerotic heart disease (CAD) in Peking Union Medical College Hospital from January 1983 to July 2021 were enrolled. According to the age of onset of coronary heart disease, the 74 patients were divided into PCAD group and NPCAD (non-premature coronary heart disease) group. T test and Chi square test were used to analyze the data of the two groups, the risk factors for AS-PCAD were analyzed by multivariate Logistic regression. Results:① There were 37 cases in the PCAD group and 37 cases in the NPCAD group. In the PCAD group, there were 28 men and 9 women; wherease all were men in the NPCAD group. The difference was statistically significant ( χ2=10.25, P=0.001). ② Compared with the NPCAD group, the age of AS-PCAD group was younger [(23±10) years vs (29±12) years, t=-2.28, P=0.026], and the course from AS to CAD was shorter [(25±10) years vs (34±13) years, t=-3.00, P=0.004], hemoglobin (Hb) level was lower [(122±23) g/L vs(132±18) g/L, t=2.10, P=0.039], rate of anemia was higher [38.5%(14/37) vs 16.2%(6/37), χ2=4.39, P=0.037]. Proportion of increased C-reactive protein (CRP) was higher [65.5%(19/29) vs 35.5%(11/31), χ2=5.41, P=0.019]. ③ Juvenile onset AS (JoAS)[ OR(95% CI)=3.45(1.31, 9.10), P=0.012] and high levels of CRP [ OR (95% CI)=3.68 (1.44, 9.40), P=0.006] might berisk factors of AS-PCAD by multiple logisctic regression analysis. Conclusion:Patients with AS have a higher probability of PCAD, especially in those patients with JoAS, persistent inflammation and anemia. It is necessary to be alert to the risk of PCAD and early screening.

Analysis of clinical manifestations at different age of onset in systemic sclerosis / 中华风湿病学杂志

Objective:To investigate the clinical and laboratory characteristics of systemic sclerosis (SSc) patients at different age of onset.Methods:Data of SSc patients with onset age ≥18 years old who were registered in the Peking Union Medical College Hospital and Chinese Rheumatism Data Center from August 2008 to June 2020 were included. Patients were divided into 3 groups by the age of onset according to the age segmentation of the World Health Organization. Counting variables were presented as frequency (percentage). Quantitative results were presented as mean±standard deviation, or median, inter quartile range. Differences between groups were analyzed by analysis of variance, the Mann-Whitney test or the chi-square test, depen-ding on the distribution of the variables.Results:Six hundred and eighty-two SSc patients were included. Accor-ding to the age of onset, they were divided into three groups: youth group (18-44 years old), middle-aged group (45-59 years old) and elderly group (over 60 years old). There were 361 patients in the youth group,245 patients in the middle age group and 76 patients in the elderly group. The mean age of onset was (43.8±12.1) years. The variables with significant different among the groups were as the following: left ventricular diastolic dysfunction [14.0%(14/100), 38.8%(39/98), 65.4%(17/26); χ2=30.756, P<0.001]; cardiac arrhythmias [1.9% (7/361), 3.7% (9/361), 7.9% (6/76), χ2=7.38, P=0.024), Raynaud's phenomenon [94.7% (342/361), 89.4%(219/245), 89.5%(68/76), χ2=6.73, P=0.035], loss of finger pad substance [36.9%(133/360), 25.4% (62/244), 18.4% (14/76), χ2=15.184, P=0.001]; digital ulcer [31.0% (112/361), 23.0% (56/244), 15.8% (12/76), χ2=9.86, P=0.007]; arthritis [16.3%(59/361), 13.5%(33/245), 5.3%(4/76), χ2=6.49, P=0.039], digital contracture [11.6%(42/361), 5.7%(14/245), 9.2%(7/76), χ2=6.10, P=0.047]; positive anti-RNP antibody [32.3% (116/359), 20.7% (50/241), 17.3% (13/75), χ2=14.06, P=0.001]; and positive anti-centromere antibody [8.9% (32/351), 18.4%(45/239), 23.7%(18/76), χ2=17.78, P<0.001] were significantly different between the young age group and elder group. Conclusion:The predominant age of disease onset of SSc is middle and young age. Elder onset SSc patients are more likely to have left ventricular diastolic dysfunction, and young onset patients are more likely to have microvascular lesions, which needs more attentions by clinicians.

Analysis of clinical characteristics in systemic lupus erythematosus patients with Libman-Sacks endocarditis / 中华风湿病学杂志

Objective:To analyze the clinical characteristics and risk factors of systemic lupus erythematosus (SLE) with Libman-Sacks endocarditis (LSE).Methods:Data of SLE patients with LSE ( n=20) who admitted in Peking Union Medical College Hospital from January 2012 to May 2021 were retrospectively collected. SLE patients without LSE ( n=60) were randomly selected as controls according to 1∶3 age and sex matched in the hospitalized patients during the same period. Clinical characteristics, laboratory and imaging examinations were analyzed. Data were expressed as Mean± SD, and t test was used to compare quantitative data in normal distri-bution. Data were expressed as M ( Q1, Q 3), and Wilcoxon signed-rank test or Wilcoxon rank sum test were used to compare quantitative data in non-normal distribution. The count data were compared with Chi-square test or Fisher's exact test. Univariate conditional logistic regression was used for univariable analyses. P values less than 0.05 were considered statistically significant. Results:There were 20 SLE patients with LSE, 18 females with an average age of (32±9) years (13 to 49 years). The disease duration of SLE was 16.04(0, 185.1) months when LSE was discovered, and vegetations were located at the mitral valve in 19 (95.0%) patients. Cerebral infarction (45.0% vs 10.0%, χ2=9.87, P=0.001) and antiphospholipid syndrome (APS) (50.0% vs 5.0%, χ2=22.32, P<0.001) were more common in SLE with LSE. In addition, SLE with LSE had lower platelet counts [(140±67)×10 9/L vs (189±115)×10 9/L, t=-2.29, P=0.026] and higher positive rate of lupus anticoagulant (LA) (80.0% vs 23.6%, χ2=19.65, P<0.001), lower positive rate of anti-SSA antibodies (21.1% vs 60.0%, χ2=6.38, P=0.012). Left atrial enlargement (anteroposterior diameter of left atrium>40 mm) was more common in SLE patients with LSE (35.0% vs 5.4%, χ2=9.37, P=0.002), and anteroposterior diameter of left atrium [(37±7) mm vs (33±4) mm, t=2.15, P=0.043] were larger and left ventricular ejection fraction [(63±10)% vs (68±6)%, t=-2.41, P=0.019] was lower. The risk of SLE with LSE complicated with APS was 19 times compared with SLE without LSE [ OR (95% CI)=19.00 (4.43, 81.38), P<0.001]. Conclusion:SLE patients with LSE have increased risk of APS and cerebrovascular diseases. For patients with positive LA, the possibility of LSE should be alerted.

A clinical analysis of 13 patients with scleroderma renal crisis and pulmonary arterial hypertension / 中华风湿病学杂志

Objective:To describe a series of systemic sclerosis (SSc) patients with the combination of scleroderma renal crisis (SRC) and pulmonary arterial hypertension (PAH).Methods:The medical records of 472 SSc patients in Peking Union Medical College Hospital between January 2012 and October 2020 were reviewed and a retrospective analysis of the characteristics of patients with SRC and PAH among SSc patients was conducted.Results:Thirteen patients suffered from SRC and PAH in the SSc patients, 1 case was limited cutaneous SSc, and 12 cases were diffuse cutaneous SSc. Five patients had renal crisis before pulmonary arterial hypertension, 4 patients had pulmonary arterial hypertension before the occurrence of renal crisis, and the remaining 4 patients were found at the same time. Among them, 11 patients had Raynaud's phenomenon, 7 had gastrointestinal bleeding, 6 had pulmonary edema and 3 had telangiectasias. Twelve cases were positive for anti-nuclear antibodies and 4 cases were positive for anti-Scl-70 antibodies. N-terminal pro-brain natriuretic peptide (NT-proBNP)>1 400 ng/L in 11 patients. Two patients had thrombotic microangiopathy (TMA). Among the 13 patients, 3 patients died during hospitalization, 2 patients were lost to follow-up, and 2 patients died within 5 years of follow-up. Six patients survived, and 1 of the 4 patients with regular dialysis were discharged from dialysis.Conclusion:In patients with scleroderma, SRC can occur earlier, later than, or at the same time with SSc-PAH. Patients may have a higher incidence of gastrointestinal bleeding and higher level of NT-proBNP. PDE5i or ERAs may be beneficial.

Sudden chest pain, painful swelling left lower limb and malar erythema / 中华风湿病学杂志

Objective:To improve the understanding of the relationship between antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE).Methods:The clinical characteristics and process of diagnosis and treatment of a case was reported and analyzed. This patient was initially diagnosed as antiphospholipid syndrome and later developed new skin lesion and positive anti-dsDNA antibody, which made the diagnosis of systemic lupus erythematosus.Results:A 15-year-old girl suffered acute pulmonary embolism, lower extremity deep vein thrombosis, and high titer of anti-phospholipid antibody, but negative for other autoantibodies. So primary antiphospholipid syndrome was diagnosed. Symptoms were improved after thrombolysis and anticoa-gulation treatment. During the follow-up period, the patient developed malar erythema, lymphocytopenia, proteinuria, positive ANA, anti-dsDNA antibody, and reduced complement level. So she was diagnosed with systemic lupus erythematosus. After glucocorticoid pulse therapy and immunosuppressants treatment, the symptoms were relieved and lupus disease activity was decreased.Conclusion:A few primary APS patients can progress into SLE. Patients with risk factors such as a younger age of onset, positive ANA and positive Coomb's test results should be closely followed up.

Recommendations for the diagnosis and treatment of connective tissue disease associated pulmonary arterial hypertension in China / 中华内科杂志

Pulmonary arterial hypertension (PAH) is a clinicopathological syndrome caused by the increase of pulmonary artery, and it is the most serious complication of connective tissue disease (CTD). In recent years, a lot of progress has been made in the diagnosis, treatment and evaluation of PAH. Chinese Rheumatology Association formulated this recommendation on the basis of current experience and guidelines, in order to promote early screening, early diagnosis and early intervention of CTD-PAH, as well as patient follow-up and management, to improve the prognosis of CTD-PAH patients.

The clinical characteristics of nuclear dense fine speckled pattern in 95 289 patients / 中华内科杂志

To investigate the distribution and clinical significance of nuclear dense fine speckled (DFS) pattern in various diseases. A total of 95 289 patients who received DFS tests at Peking Union Medical College Hospital from January 2019 to December 2020 were included in this study. The results of indirect immunofluorescence assay (IIF) for detection of antinuclear antibody (ANA) were evaluated. The positive rates of ANA and DFS were 39.60% (37 733/95 289) and 1.19% (1 139/95 289) respectively. The positive rate of DFS in ANA-positive patients was 3.02% (1 139/37 733). DFS and ANA positivity were significantly different among different age groups rather than gender. The positivity rate of DFS reached the peak (55.57%, 633/1 139) in young patients between 21-40 years, while positive ANA with negative DFS was mainly observed in patients between 41-60 years (37.26%, 13 636/36 594). Additionally, single ANA-positivity were mainly detected in rheumatology department (59.23%, 18 402/31 066), whereas positive DFS was more common in obstetrics and gynecology department (3.08%, 49/1 593). There were 82.88% (944/1 139) patients with positive DFS diagnosed with non-autoimmune disease (non-AID), and 19.49%(222/1 139) with dermatosis. Positive DFS with higher titer (≥1∶320) was detected more frequently in autoimmune disease (AID) patients (5.13%, 10/195) than in non-AID patients (1.69%, 16/944) ( P<0.05). The DFS pattern is rare in ANA positive patients, which is mainly observed in women between 21-49 years. High titer of DFS is prevalent in AID patients, but positive DFS is detected more in non-AID patients, especially those with dermatosis.

The 498th case: rash, fever and hematuria / 中华内科杂志

A 50-year-old man was admitted to the Department of Rheumatology at Peking Union Medical College Hospital with rash for 6 months, and fever and hematuria for 5 months. The main clinical manifestations included fever, fatigue, purpura, hematuria and thrombocytopenia. He was positive for antinuclear antibody (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and rheumatoid factor (RF), and had low complement levels. Initial blood culture, echocardiography and chest CT showed no signs of infection. Diagnosis of connective tissue disease was made initially. His disease improved under treatment with glucocorticoids and immunosuppressive agents, but relapsed when glucocorticoids were tapered. After admission, the diagnosis was reconsidered, and infective endocarditis was finally diagnosed with repeated positive blood cultures and vegetations detected by transesophageal echocardiography. Amoxicillin and clavulanate potassium were initiated, and surgery was performed. His symptoms finally recovered gradually.

Association of skin lesion severity with clinical features of psoriatic arthritis / 中华内科杂志

Objective:To investigate the relationship between psoriasis severity and clinical features in psoriatic arthritis (PsA).Methods:Patients were recruited from the Chinese REgistry of Psoriatic ARthritis (CREPAR) between December 2018 and June 2021, and data were collected including the baseline demographic characteristics, various clinical manifestations (including arthritis, nail disease, comorbidities), laboratory tests[including erythrocyte sedimentation rate(ESR), C-reactive protein (CRP)], health assessment questionnaire (HAQ). Body surface area (BSA) and psoriasis area and severity index (PASI) were selected for the tools of assessment of cutaneous psoriasis. Patients were divided to two groups, including the severe psoriasis group (BSA>10%) and the non-severe psoriasis group (BSA≤10%). Disease assessment included ankylosing spondylitis disease activity score (ASDAS), disease activity score 28 (DAS28) and disease activity in psoriatic arthritis (DAPSA).Results:1 074 eligible patients with PsA were recruited, and 106 (9.9%) had severe psoriasis. Compared with non-severe psoriasis group, the severe psoriasis group had more peripheral joint involvement (including patients with ever or current peripheral arthritis, 94.3% vs. 85.6%), more polyarticular joint involvement (including patients with current peripheral arthritis, 74.0% vs. 58.2%), more axial joint involvement (51.4% vs. 39.9%), more nail disease (72.6% vs. 61.4%), more frequency of smoking (20.2% vs. 18.7%), and higher proportion of hypertension (23.4% vs. 14.4%). In addition, the severe psoriasis group had higher level of ESR [33(10, 70) mm/1h vs. 20(9, 38) mm/1h] and CRP [18.6(5.0, 60.8) mg/L vs. 7.0(2.4, 18.1) mg/L], higher values of DAS28-ESR (4.5±1.7 vs. 3.7±1.5), DAS28-CRP (4.2±1.5 vs. 3.4±1.4), ASDAS-ESR (3.5±1.4 vs. 2.6±1.2), and ASDAS-CRP(3.4±1.6 vs. 2.5±1.2), higher scores of HAQ [0.6(0.1, 1.0) vs. 0.3(0.0, 0.8)].Conclusion:Patients with PsA with severe psoriasis bore a heavier disease burden. Therefore, clinicians were supposed to pay more attention to them. In addition to skin lesions, they should also focus on examination of other clinical manifestations, such as joints and nails.

The 490th case: arthralgia, amenorrhea, aphasia / 中华内科杂志

A 25-year-old woman was admitted to Peking Union Medical Hospital presented with arthralgia for 5 years, amenorrhea for 16 months, and speech disorder for 3 months. This patient has been afflicted by intermittent pain in metacarpophalangeal and proximal interphalangeal joints of both hands for 5 years. Her menstruation has been irregular 1 year ago and rapidly progressed to amenorrhea. Laboratory tests revealed postmenopausal sex hormones levels (estradiol<5 ng/L, follicle-stimulating hormone 62.5 IU/L, luteinizing hormone 58.71 IU/L) and no antral follicles were seen in gynecologic ultrasound. She was diagnosed with premature ovarian failure and treated with hormone replacement therapy, still with no ovulation. Numbness and weakness of right arm has recurrently occurred to her 4 months ago, and persistent weakness of right limbs combined with motor speech disorder occurred 1 month later. Magnetic resonance angiography was suggestive of ischemic stroke. Hormone replacement therapy was discontinued. Comprehensive laboratory tests revealed positive anti-dsDNA, anti-SSA/SSB, anticardiolipin and anti-β 2GPⅠ antibodies. Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) was diagnosed. Since no drug with gonadal toxicity had been applied to the patient before, her amenorrhea was considered to be due to autoimmune oophoritis secondary to SLE. After treated with high-dose glucocorticoid, mycophenolate mofetil and hydroxychloroquine for 4 months, her menstruation recurred and regularly occurred till now. In some cases, amenorrhea in SLE patient might be resulted from autoimmune oophoritis associated with lupus flare, instead of use of drug with gonadal toxicity.

Clinical characteristics and pregnancy outcomes of non-criteria obstetric antiphospholipid syndrome / 中华内科杂志

Objective:To study clinical characteristics and pregnancy outcomes under anti-coagulation therapy of non-criteria obstetric antiphospholipid syndrome.Methods:Patients suspected of obstetric antiphospholipid syndrome(OAPS) were recruited through Chinese Rheumatism Data Center from 2015 to 2019 consecutively. Patients fulfilling 2006 Sydney revised antiphospholipid syndrome criteria were classified as OAPS. Patients fulfilling definition of non-criteria OAPS(NCOAPS) by expert consensus on diagnosis and management of obstetric antiphospholipid syndrome of China were classified as NCOAPS. Clinical characteristics and laboratory results of two groups were compared. Live birth rates and pregnancy outcomes under anti-coagulation therapy were studied.Results:A total of 88 patients were enrolled, including 56 patients (63.6%) as OAPS, 32(36.4%) as NCOAPS. Live births were only reached in 16.1% (9/56) in OAPS patients and 12.5%(4/32) in NCOAPS. Fetal losses after 10 weeks of gestation and pre-eclampsia before 34 weeks were more common in OAPS group compared to NCOAPS group [78.6%(44/56) vs. 18.8%(6/32), P<0.001; 25.0%(14/56) vs. 3.1%(1/32), P=0.020, respectively]. After enrollment, 15 pregnancies were recorded in OAPS, 10 in NCOAPS, all of whom were treated with low-dose aspirin (LDA) combined with low-molecular weight heparin (LMWH). Live birth rates saw dramatic improvements compared to baseline levels in OAPS [16.1% (9/56) vs. 11/15] along with NCOAPS [12.5% (4/32) vs. 7/10]. Conclusion:Though NCOAPS and OAPS patients differ in antiphospholipid antibody spectrum and pattern of pregnancy morbidities, both groups benefit from LDA combined with LWMH treatment, as live birth rates improve. Non-criteria OAPS patients are recommended to receive anti-coagulation therapy during pregnancy.

Clinical characteristics and risk factors in 118 patients with systemic lupus erythematosus and osteonecrosis / 中华内科杂志

Objective:To investigate the clinical characteristics and risk factors for osteonecrosis (ON) in patients with systemic lupus erythematosus (SLE).Methods:This is a case-control study. A total of 118 patients diagnosed with SLE complicated with ON (study group) were retrospectively analyzed between 2014 and 2019. Gender, age, and course matched 118 SLE patients without ON were selected as controls. Clinical manifestations, laboratory findings, medical history, and treatments were recorded and analyzed.Results:Among 118 patients, the male to female ratio was 20 to 98 with a median age of 27 years and course of disease 1-168 months. Compared with the control group, the study group presented a longer cumulative duration of glucocorticoid therapy [36.5 (0-168) months vs. 19.0(0-168) months on average, P<0.05], a higher incidence of osteoporosis (29.7% vs. 4.2%, P<0.001), a higher frequency of immune-suppressive therapy (83.9% vs. 64.4%, P=0.035), more organs involveed [median 2 (0-5) vs. 1 (0-4)], and a higher SLE disease activity index (SLEDAI) (14.22±7.40 vs. 11.63±6.11, P<0.05) in univariate logistic regression. The control group had a higher rate of positive Coombs test (39.8% vs. 7.6%, P<0.05). No statistical difference on methylprednisolone (MP) pulse therapy ( P>0.05) was observed. Multivariate logistic regression suggested that SLEDAI ( OR= 1.070, 95% CI 1.026-1.116, P<0.005), osteoporosis ( OR=10.668, 95% CI 3.911-29.103, P<0.001) and a positive Coombs test( OR=0.492, 95% CI 0.266-0.910, P<0.05) were related to the development of ON in SLE patients. Conclusion:A higher disease activity and the presence of osteoporosis are associated with an increased risk of ON in patients with SLE, and positive Coombs test seems a protective factor of ON.