Background Waardenburg syndrome type 2 (WS2) has been reported to be a rare hereditary disorder, which is distinguished by vivid blue eyes, varying degrees of hearing impairment, and abnormal pigment deposition in the skin and hair. Variants in the sex-determining region Y-box containing gene 10 (SOXl0) gene may cause congenital deafness and have been demonstrated to be important during the development of WS2. Methods Complete clinical data of the proband and her family members (her parents and 2 sisters) was collected and physical examinations were performed in the hospital. The laboratory examination including hemoglobin, Coomb's test, urine protein, ENA, autoimmune hepatitis-related autoantibodies and ultrasonography were all conducted. We obtained the peripheral blood samples from all the participants and performed whole exome sequencing and sanger sequencing validation. Results The present study identified a family of 5 members, and only the proband exhibited typical WS2. Beyond the characteristics of WS2, the proband also manifested absence of puberty. The proband and her younger sister manifested systemic lupus erythematosus (SLE). Whole exome sequencing revealed a de novo variant in the SOX10 gene. The variant c.175 C > T was located in exon 2 of the SOX10 gene, which is anticipated to result in early termination of protein translation. Conclusion The present study is the first to report a case of both WS2 and SLE, and the present findings may provide a new insight into WS2.

Background: POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a kind of plasma cell disease with complex clinical manifestations involving multiple systems. Metal poisonings through a mucocutaneous are rare in clinic and reported less in the literature. People may exposure to toxic metals through air, food, water, or inappropriate use of drugs. Acute or chronic poisonings can lead to various toxic effects on body tissues and organs. Both POEMS syndrome and heavy metal intoxication are uncommon with multifarious and nonspecific clinical manifestations. Here we describe a case of a 54-year-old man with polyarticular pain and IgA lambda type monoclonal protein in his serum. The diagnosis was confirmed by heavy metals testing in his urine and the herbal mixtures he took. This is the first available report of arsenic and mercury intoxication mimicking POEMS syndrome.

BackgroundAn outbreak of coronavirus disease 2019 (COVID-19) started in December, 2019. The epicentre, Wuhan in Hubei Province, was in lockdown. From Jan 23, 2020, most hospitals in Wuhan only focused on patients with COVID-19, and patients with chronic diseases could not visit their physicians in clinic and had no access to prescriptions. Smart System of Disease Management (SSDM) is a series of mobile applications for chronic disease management that includes both patient and physician interfaces. After training in clinic, patients regularly do a disease activity assessment, and input data from lab tests as well as their medication. The data is then synchronised to the mobile of the responsible physician. The physician can then do an online consultation and renew prescriptions on the basis of real-time data from his or her patients. We aimed to establish the feasibility and effects of SSDM in maintaining effective interactions between patients and physicians in Hubei province during the COVID-19 epidemic period.MethodsBased on the SSDM database, we did a multicentre retrospective cohort study of patients with rheumatic disease in Hubei province in China. SSDM had been widely used across China since 2015. To study the influence of interruption of routine care by the COVID-19 epidemic for patients with rheumatic disease, we included patients registered with SSDM from Hubei Province. Data on patient disease activities, online consultations, and prescription refilling, as well as surveys on satisfaction about the online service were extracted from Jan 23, 2020 to Feb 27, 2020, acting as the study group, and data from the same period during 2018 and 2019 were also extracted as a control. Inclusion criteria included a confirmed diagnosis of rheumatic disease and disease duration of at least 3 months. Patients were excluded from the study if they declined participation or discontinued before completion of the survey. For patients with rheumatoid arthritis, achieving a disease activity score with 28 joints (DAS28) of less than 3·2 was considered to be a treat-to-target (T2T) status. For patients with systemic lupus erythematosus, a disease activity index-2000 (SLESAI-2K) score of less than 4 was the main target of the lupus low disease-activity state (LLDAS). We compared the T2T and LLDAS prevalence during the epidemic period of 2020 with that of 2018 and 2019. All statistical analyses were done with Python version 3.7.4. We used descriptive and frequency statistics (percentage) to describe baseline demographic information and clinical information. Comparison of ratio variables between two groups was done with a χ2 test.FindingsBy Feb 27, 2020, a total of 173 560 adult patients (46 861 [27%] men and 126 699 [73%] women) with rheumatic disease from 860 hospitals across China registered and routinely used SSDM since 2015. Patients were encouraged to upload their data and do a disease activity self-assessment every 1–3 months. 10 441 (6%) of 173 560 patients (3237 [31%] with rheumatoid arthritis and 1566 [15%] with systemic lupus erythematosus) were managed by 176 rheumatologists from 42 hospitals in Hubei province. From Jan 23, 2020 to Feb 27, 2020, 69 rheumatologists from 28 hospitals provided 1451 patients with 1692 consultations and supplied 566 (39%) of them with continued medication, which included 55 commonly used therapeutic drugs for rheumatic diseases. 247 (8%) of 3237 patients with rheumatoid arthritis during the 2020 epidemic and 350 (9%) in same period during 2018 and 2019 did the DAS28 self-assessments, and T2T was 47% in 2020 compared with 50% in 2018 and 2019, (p=0·53). 293 (19%) of 1566 patients with systemic lupus erythematosus in 2020 and 210 (16%) in 2018 and 2019 did the SLESAI-2K self-assessments, and LLDAS was 60% in 2020 compared with 47% in 2018 and 2019 (p=0·03). Surveys showed that 100% of patients were satisfied with the interactions, which prevented the risk of cross-infection and discontinuation of medication.InterpretationPatients with rheumatism can maintain accessibility to good care in the era of the COVID-19 epidemic by using SSDM for consultations and medication refills. The clinical outcomes, at least for both rheumatoid arthritis and systemic lupus erythematosus, are not compromised.FundingNone.

Background: Behcet´s disease (BD) is a systemic autoimmune disease that affects multiple organ systems with recurrent oral ulcers, genital ulcers and skin lesions. Behcet´s Disease Current Activity Form (BDCAF) and Electronic Medical Record-based Activity Index (EMRAI) are commonly used internationally to evaluate the disease activity of BD. Objectives: This study aimed to analyze the clinical characteristics, the level of disease activity, and the incidence of anxiety and depression for Chinese BD patients. Patients can perform self-management of disease with SSDM. Methods: SSDM is a series of doctor-patient interactive applications for self-management of patients with chronic diseases. Patients can perform self-assessment with SSDM and upload the data to their authorized doctors. The SSDM patients’ application system integrates the BDCAF and EMRAI into one scoring system. Patients could obtain scores of BDCAF and EMRAI by responding to one questionnaire through SSDM. Results: From Apr 2017 to Jan 2020, 719 BD patients from 166 hospitals used SSDM, with a mean age of 38.97±12.71 (14~81) years old, and median disease duration of 20.8 months. 719 patients performed BDCAF and EMRAI self-assessment 1321 times, 252 patients repeat assessments for 855 times. The mean score of BDCAF and EMRAI are 3.57±2.17 and 3.44±1.90, respectively. The matching degree of the two score was 0.8747. The most common clinical characteristics were oral ulcers (83.73%), ocular symptoms (62.03%), joint pain (50.07%). The comparative study between males and females revealed significant difference in the aspects of epididymitis (10.94% vs 0, p<0.001), genital ulcer (35.09% vs 44.93%, p=0.01), headache (24.15% vs 33.92%, p=0.01) and superficial thrombophlebitis (24.15% vs 33.92%, p=0.01). Table 1. Table 1. Clinical Characteristics of different systems in Chinese BD patients. Presence of clinical characteristics Total Males Females P value Oral ulcer 83.73% (602) 86.42% (229) 82.16% (373) 0.14 Genital ulcer 41.31% (297) 35.09% (93) 44.93% (204) 0.01* Epididymitis 4.03% (29) 10.94% (29) 0 (0) <0.001** Erythema 29.49% (212) 29.43% (78) 29.52% (134) 0.98 Skin lesions 26.84% (193) 28.68% (76) 25.77% (117) 0.4 Superficial thrombophlebitis 30.32% (218) 24.15% (64) 33.92% (154) 0.01* Headache 30.32% (218) 24.15% (64) 33.92% (154) 0.01* Joint pain 50.07% (360) 51.32% (136) 49.34% (224) 0.61 Arthritis 14.60% (105) 14.72% (39) 14.54% (66) 0.95 Gastrointestinal involvement 24.90% (179) 27.92% (74) 23.13% (105) 0.15 Ocular symptoms 62.03% (446) 62.64% (166) 61.67% (180) 0.79 Nervous involvement 23.78% (171) 25.66% (68) 22.69% (103) 0.37 Vascular involvement 15.72% (113) 18.11% (48) 14.32% (65) 0.18 *P values are for the comparison between the males and females. Conclusion: Chinese BD patients can effectively perform BDCAF and EMRAI self-assessment with SSDM. The results of the assessment conducted by the two scoring systems are similar. The clinical characteristics of Chinese BD were different depending on gender. Acknowledgments: : Smart system of disease management (SSDM) was developed by Shanghai Gothic Internet Technology Co., Ltd. Disclosure of Interests: None declared

类风湿关节炎(rheumatoid arthritis,RA)是一种器官特异性自身免疫病,本病的免疫调节失衡可导致嗜酸粒细胞增多.现将我科诊治的1例报告如下. 临床资料 患者女,68岁,因“关节肿痛20余年,加重20 d”于2008年5月16日入住华中科技大学同济医学院附属同济医院.患者20余年前无明显诱因出现关节肿痛,主要累及双侧肩关节及膝关节,当地医院诊断为类风湿关节炎,给予泼尼松5 mg,2次/d,口服治疗,疼痛可缓解.20年来,上述症状反复发作.

Background: Combination therapy with DMARDs for treating RA is standard of care. However, certain rates of adverse events (AEs) are unavoidable. The stigmas are how to predict the risk and how to define drug withdraw sequence if AEs persist for optimal risk reductions. The decisions made are always empirically. Objectives: To develop a risk prediction model and an algorithm for drug withdraw sequence based on data mining from the SSDM. Methods: SSDM is an interactive mobile disease management tool, including two application systems (APPs) for both the doctors and the patients. The patients can input medical records (including medication and laboratory test results) and perform self-evaluation (DAS28, HAQ) via App. The data synchronizes to mobiles of authorized rheumatologists through cloud and advices could be delivered. In previous studies, we demonstrated that patients could master SSDM after training. In order to develop a prediction model and the master algorithm, abnormal white blood cell counts (WBC) and alanine aminotransferase (ALT) elevation were targeted. Data was collected, extracted, validated, and Bayesian networking, data mining, modeling were performed. WBC under 4k/ml is defined as leukocytopenia (LP), over 10k/ml as infection predisposing (IP), and ALT > 40 U/L as ALT elevation. Results: From Jun 2014 to Jan 2019, 44,533 RA patients from 587 centers registered in SSDM. 135 different drugs and 882 combination therapies are identified. LP happens at 317 and IP at 286, ALT at 322 cases in 641 treatment regiments. Among them, MTX based regiments are 257 types, and the risk ratio (RR) are profiled as prediction model by comparing each AE rate of combination regiment with that of MTX monotherapy (Fig 1). The RR ranges from 0.28 to 6.28. The highest risk combination of prednisone (Pred), leflunomide (LEF), methotrexate (MTX), hydroxychloroquine (HCQ) and Celecoxib is selected (RR=6.28) to develop a master algorithm. Figure 2 shows Bayesian network, in which, quartet correlaties with 31 different regiments. Based on Bayesian method, the probabilities of LP, IP and ALT are plotted through 64 modeling, and the algorithm for drug withdraws strategies is generated. Drug withdrawing sequence for LP is HCQ, then Cel, then LEF, then Pre, the risks of LP are reduced by 41%, 22% 36% and 15%, respectively. For IP, withdraw sequence is Pred, then LEF, then Cel, then HCQ, the risks of IP are reduced by 45%, 28%, 23% and 4%, respectively, For ALT, withdraw sequence is MTX, then Pred, LEF, then Cel, the risks of ALT are reduced by 48%, 8%, 7%and 6%. Conclusion: Through patterns extraction, data mining, modeling, and Bayesian networking, a risk prediction model and a master algorithm for drug withdraw strategy in reduction of AEs are developed, which are expendable and replicatablei. Via continuing data inputs and machine leaning, an artificial intelligent system in assisting clinical forecast and decision-making may be achieved with SSDM. Disclosure of Interests: None declared

Objective:To determine the value of serum α1-acid glycoprotein (AAG) for estimating the activity of rheumatoid arthritis (RA) in patients treated with biological DMARDs.Methods:A total of 84 RA patients treated with etanercept or tocilizumab for at least 24 weeks were included in this study.According to the clinical disease activity index (CDAI) at 24 weeks,they were then divided into low disease activity (CDAI ≤ 10) and medium or high disease activity (CDAI ＞10) groups.Serum levels of AAG,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) were analyzed after treatment.Results:Of the 41 etanercept-treated patients,18 were in low activity group and 23 in medium or high disease ac tivity group.Of the 43 tocilizumab-treated patients,22 patients were in CDAI ≤ 10 group and 21 in CDAI ＞ 10 group.AAG,ESR,hsCRP,CDAI and disease activity score 28 (DAS28)-ESR were all significantly decreased in low disease activity group as compared with those in medium or high disease activity group after treatment (P ＜ 0.001),regardless treatment with etanercept or tocilizumab.For patients treated with etanercept,AAG,ESR,hsCRP,CDAI and DAS28-ESR had no significant change in medium or high disease activity group.For tocilizumab-treated group,CDAI and DAS28-ESR had no significant change in medium or high disease activity group as compared with baseline,however,AAG,ESR and hsCRP were reduced significantly.Conclusion:AAG can be considered as a reliable marker for evaluating the disease activity in RA patients treated with etanercept.However,for patients treated with tocilizumab,AAG may not exactly reflect disease activity.

Ye, Cong MD, PhD2; Geng, Zhe MD, PhD1; Li, Shouxin MD, PhD2; Yu, Fei MD, PhD2 Author Information

Objective To investigate the value of neutrophil-to-lymphocyte ratio (NLR) for estimating treatment response of tocilizumab(TCZ) therapy in rheumatoid arthritis (RA). Methods Sixty RA patients treated with TCZ for more than 24 weeks were divided into stable group(41 cases) and flare group( 19 cases) according to disease activity after TCZ treatment. NLR, erythrocyte sedimentation rate (ESR), C-reactive protein(CRP) and clinical disease activity index (CDAI) were compared before and after treatment between the two groups and between stable and flare period in flare group. Results Gender,age,disease period, NLR, ESR, CRP and CDAI were not significantly different between the two groups at baseline ( P > 0.05 ). Compared with before TCZ therapy, NLR, ESR, CRP and CDAI all decreased significantly after therapy in the two groups during stable period ( P < 0.05 ). However, there were no significant differences of these indexes between the two groups during stable period ( P > 0.05 ). Compared with stable period in flare group, swollen joint count, tender joint count, CDAI, ESR, neutrophil count and its percentage as well as NLR all increased during flare period, while percentage of lymphocyte decreased(P <0.05 ). CRP, PLT, hemoglobin and percentage of lymphocyte did not change significantly (P >0.05 ). 68.4% (13/19) and 57.9% (11/19) of patients during flare period in flare group had higher ESR and CRP respectively. 21.1% (4/19) of them had lower neutrophil count and 47.4% (9/19) had higher lymphocyte count. 94.7% (18/19) of them had higher NLR,and CDAI increased in all of them. Conclusion Compared with CRP and ESR, NLR can be considered as a less expensive, but more convenient,reliable and objective marker for evaluating disease activity in RA patients treated with TCZ along with CDAI.

Objective To evaluate the safety and drug adherence of tocilizumab(TCZ)in patients with moderate to severe rheumatoid arthritis(RA)in routine clinical practice. Methods This 24 week single center observational study recruited patients with moderate to severe RA. Therapy adherence rate was calculated by actual dosing/expected dosing×100%. Efficacy end points included physician global assessment of disease activity(PGA),patient global assessment of disease activity(PtGA),28-joint disease activity score(DAS28)and so on. Safety was evaluated by recorded adverse events (AEs). Results Sixty patients were enrolled with a mean (SD) treatment adherence of (67±27)%. PGA, PtGA, pain assessment (VAS), TJC and SJC all decreased during this study. At the 12th week, 25%(6/24) and 29%(7/24) of the patients achieved DAS28 remission and EULAR good response,respectively.Eighteen AEs were recorded,of which only 2 were severe AEs(SAEs)and neither was related to TCZ. Conclusion TCZ is a highly safe treatment for decreasing disease activity in patients with moderate to severe RA in China.However,drug adherence still need to be improved.

Objective To establish a point-scoring diagnostic system for Sjögren's syndrome (SS) based on quantified SPECT imaging of salivary gland, and evaluate its feasibility and performance compared with 2002 AECG criteria and 2012 ACR criteria. Methods 213 patients with suspected SS enrolled in this study. The related clinical data of all patients were collected. All patients were evaluated and grouped on a clinical basis and posttreatment follow-up by rheumatology specialists as the unified standard (SS group with 149 cases and nSS group with 64 cases). From SPECT imaging of salivary gland, Tmax, UImax, Ts and EFs were derived for bilateral parotid and submandibular glands, and compared between the groups. A point-scoring diagnostic system for SS was established based on the quantified SPECT imaging of salivary gland. We estimated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the new diagnostic system, compared with 2002 AECG criteria and 2012 ACR criteria. Results When 7.0 was used as the cut-off point, the sensitivity, specificity, PPV, NPV and accuracy for the new point-scoring system in diagnosing SS were 89.93% (134/149), 93.75% (60/64), 97.10% (134/138), 80.00% (60/75) and 91.08% (194/213), respectively. The new point-scoring diagnostic system based on quantified SPECT imaging of salivary gland keeps the specificity comparatively to 2002 AECG criteria and 2012 ACR criteria, but improves the sensitivity significantly (P<0.01). Conclusion The new point-scoring diagnostic system for SS based on quantified SPECT imaging of salivary gland may be superior to 2002 AECG criteria and 2012 ACR criteria, with higher sensitivity and similar specificity in the diagnosis of SS. Additionally, it also has good feasibility in the clinical settings.

Although the development of the 2009 Sp A classification criteria by Assessment of Spondylo Arthritis international Society(ASAS) represents an important step towards a better definition of the early disease stage particularly in axial spondyloarthritis(ax Sp A), the specificity of the criteria has been criticized these days. As the commonest zoonotic infection worldwide, human brucellosis can mimic a large number of diseases, including Sp A. This study was performed to determine the frequency of rheumatologic manifestations in patients with brucellosis and the chance of misdiagnosing them as having ax Sp A in central China. The results showed that clinical manifestations of ax Sp A could be observed in brucellosis. Over half of patients had back pain, and one fifth of the patients with back pain were less than 45 years old at onset and had the symptom for more than 3 months. Two young males were falsely classified as suffering from ax Sp A according to the ASAS criteria, and one with MRI proved sacroiliitis was once given Etanercept for treatment. Therefore, differential diagnosis including human brucellosis should always be kept in mind when applying the ASAS criteria, even in traditionally non-endemic areas.

OBJECTIVES:To compare the serum levels of high mobility group box chromosomal protein 1 (HMGB1) between patients with AS and healthy controls, and evaluate its association with disease activities and functional abilities; to investigate the cell surface receptors related to HMGB1 in AS patients.METHODS:The HMGB1 serum levels from71 previously untreated AS patients and 40 healthy controls were detected by ELISA method. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI), erythrocytesedimentationrate (ESR), and C-reactive protein (CRP) levels were assessed on these participants. The mRNA expression of HMGB1 and its relevant cell surface receptors RAGE, TLR2, TLR4, and IL-1Racp complex were analysed by RT-PCR.RESULTS:The HMGB1 serum levels from AS patients were significantly higher than those from healthy controls and remarkably positive correlated with BASDAI, ASDAS, BASFI, CRP, and ESR. ASDAS showed more correlated to HMGB1 serum levels than BASDAI. Besides, the expression of TLR2, TLR4, and IL-1Racp from PBMCs revealed significant correlations with the expression of HMGB1.CONCLUSIONS:HMGB1 might be a good laboratory index for the evaluation of disease activities and disease severity in AS patients. Further, extracellular HMGB1 play its inflammatory role mainly via the expression of cell surface receptors TLR2, TLR4 and IL-1RAcP complex.

患者,女性,40岁.因"对称性多关节肿痛、双下肢皮疹伴视力下降半年余"于2012年9月12日入院.患者于2012年3月无明显诱因出现双下肢散在皮疹,大小约为5 mm×5 mm,色暗红,高出皮面,压之不褪色,表面无破溃,并双腕关节、掌指关节、双踝关节轻度肿胀,伴晨僵,无发热、口腔溃疡、脱发、雷诺征象.双眼视力下降,无黑朦、重影及飞蚊症,于本院眼科门诊检查为"右眼裂孔闭锁,继发性右眼青光眼,双眼前葡萄膜炎",给予对症治疗(具体不详),眼部及皮肤关节症状无明显缓解.

目的 探讨系统性红斑狼疮(SLE)伴发严重难治性血小板减少的治疗策略.方法 分析3例系统性红斑狼疮并严重难治性血小板减少患者的临床资料,并就治疗方案的选择进行讨论.结果 3例患者均为女性,年龄范围28 ～ 38岁.1例严重血小板减少出现在SLE确诊5年后,1例为SLE的首发症状,另1例先有自身免疫性溶血性贫血,外科手术后出现明显的Evans综合征而诊断SLE.3例患者均对常规的大剂量甲泼尼龙和环磷酰胺冲击治疗以及静脉应用免疫球蛋白治疗无效,但对达那唑、小剂量环孢素和利妥昔单克隆抗体联合治疗或脾切除有所反应.结论 对于常规治疗无效的SLE伴发严重难治性血小板减少的患者可采用小剂量多药联合治疗或脾切除.

目的 了解心肌肌钙蛋白Ⅰ升高常见的原因并分析其在各类疾病中的意义.方法 回顾性分析我院2007年1月～2007年12月收治的237例心肌肌钙蛋白Ⅰ明显升高患者的临床资料.结果 心肌肌钙蛋白Ⅰ升高的常见病因依次为急性冠脉综合征(73.4%)、脑血管意外(5.5%)、慢性阻塞性肺疾病合并呼吸衰竭(3.4%)、慢性肾功能不全(2.5%)、心肺复苏后(2.1%)、感染性休克(2.1%)、肥厚型心肌病(1.3%)和高血压性心脏病(1.3%),其他各种原因引起者占8.4%.结论 心肌肌钙蛋白Ⅰ的异常升高提示心肌损伤,急性冠脉综合征是心肌肌钙蛋白Ⅰ升高的主要原因,且多种原因可以引起心肌肌钙蛋白Ⅰ的异常升高,临床上需要注意鉴别.