BACKGROUND:VEXAS syndrome is a severe autoinflammatory disease characterized by systemic inflammation, rheumatic manifestations, and hematologic abnormalities. Its clinical heterogeneity and overlap with other conditions complicate diagnosis. No case series have been reported from China. This study aimed to (1) describe the clinical features of Chinese patients with VEXAS syndrome and (2) propose screening recommendations to facilitate earlier identification. METHODS:We conducted a retrospective cohort study at Peking Union Medical College Hospital, enrolling 57 male patients with unexplained systemic inflammation and hematologic abnormalities. UBA1 gene sequencing was performed using bone marrow or peripheral blood samples. Clinical and laboratory data were extracted from electronic medical records. A screening model was developed using LASSO regression based on core features of confirmed cases and externally validated in two independent cohorts undergoing UBA1 sequencing. RESULTS:Among 57 suspected cases, 21 carried pathogenic UBA1 variants. Compared with non-VEXAS patients, VEXAS patients more frequently showed older age at onset, skin lesions, chondritis, macrocytic anemia, and characteristic bone marrow vacuolization. Importantly, skin lesions were the initial presenting symptom in over half of VEXAS patients, whereas fever predominated in the non-VEXAS group. Rare manifestations included glomerulonephritis, acute cerebral infarction, and pulmonary arterial involvement. A novel UBA1 variant (p.Thr318Met) was also identified. A screening model incorporating age at onset, skin lesions, chondritis, macrocytic anemia, and bone marrow vacuoles demonstrated good sensitivity and specificity in an external validation cohort. CONCLUSION:This study is the first to characterize the clinical features of VEXAS syndrome in a Chinese population and to delineate its phenotypic spectrum. The proposed screening tool provides a practical aid for clinicians in identifying suspected cases and may facilitate improved diagnostic pathways and patient outcomes.

Monoclonal gammopathy of clinical significance (MGCS) refers to disorders in which small B-cell or plasma-cell clones produce pathogenic monoclonal immunoglobulins that cause organ injury independent of tumor burden. Because the clinical spectrum is heterogeneous and diagnostic criteria remain evolving, MGCS is frequently underrecognized, particularly when organ manifestations precede detectable paraproteinemia. We report a 52-year-old man with multisystem manifestations including cutaneous xanthomatosis, inflammatory myopathy, cryoglobulinemia, and possible cardiac involvement. The patient initially presented with progressive polymyalgia, leukopenia, and yellow-brown cutaneous plaques. Immune abnormalities had been documented several years before detection of monoclonal protein. Laboratory evaluation revealed IgG-λ monoclonal gammopathy with type I cryoglobulinemia, complement consumption, and autoantibody positivity, indicating systemic immune activation. Bone marrow examination demonstrated only 1.4% λ-restricted clonal plasma cells. Skin biopsy confirmed xanthomatous infiltration, while muscle biopsy showed myopathic changes without amyloid deposition. Cardiac imaging demonstrated asymmetric septal hypertrophy with patchy late gadolinium enhancement. Treatment with bortezomib–cyclophosphamide–dexamethasone led to marked clinical improvement, including resolution of myalgia, regression of skin lesions, normalization of leukopenia, and disappearance of cryoglobulins, although low-level paraprotein persisted. This case highlights that immune-mediated organ injury may precede measurable clonal expansion in MGCS and supports the concept that pathogenic monoclonal immunoglobulins can act as immune effectors driving systemic inflammation.

BACKGROUND:Gout is the most common inflammatory arthritis worldwide, but doctors have a relatively poor understanding of gout that affects optimal management. There is only limited knowledge about medical students' understanding of gout. Therefore, the aim of this study was to investigate medical students' perceptions of gout and hyperuricemia. METHODS:This was a cross-sectional, questionnaire-based study conducted in June 2022 among Chinese medical students, primarily from four colleges in different geographic regions. Participants were asked to complete a 27-question survey on demographics, gout-related perception questions (derived from previous surveys), and attitudes toward gout and its management. Knowledge and perceptions of gout and associated factors were analyzed. RESULTS:The median score on the 11 gout-related perception questions was 8.0 (interquartile range 6.0-8.0). Medical students showed a relatively high accuracy in identifying the relationship between gout and hyperuricemia, as well as the clinical manifestations of gout. However, their performance varied in questions related to gout management and was notably poor in areas concerning urate-lowering therapy and drug-induced hyperuricemia. Students with clinical exposure, interest in gout-related specialties, or prior interaction with patients with gout or hyperuricemia demonstrated higher perception scores. Additionally, the source of information significantly influenced students' understanding of gout. CONCLUSIONS:Chinese medical students exhibit insufficient understanding of gout and hyperuricemia. Future initiatives to improve gout education should prioritize instruction on urate-lowering therapy and guide students to actively consult clinical guidelines.

Objectives: Deficiency of adenosine deaminase 2 (DADA2) is a rare disease with varying phenotypes and disease outcomes. We evaluated the treatment of DADA2 and explored the factors associated with disease outcome. Methods: A systemic literature review of DADA2 was conducted. Cases were included if they had documented detailed genotypes, phenotypes, treatment protocols, and outcomes. Patients were categorized as having uncontrolled and controlled disease. Factors associated with disease outcome were analyzed using logistic regression models. Results: The study population comprised 242 DADA2 patients with data on treatment protocols and responses, of whom 17 required no treatment. Tumor necrosis factor a inhibitors (TNFi) were effective in 78.6% (103/131). Hematological abnormalities and increased acute phase reactants are independently associated with the effectiveness of TNFi (OR, 0.21 [95%CI, 0.07-0.661; P=.007] and 9.62 [95%CI, 2.31-40.00; P=.002, respectively). Among the 225 patients requiring active treatment, 157 (69.8%) had controlled disease and 68 (30.2%) uncontrolled disease. Neither age of disease onset nor genotype was associated with disease outcome. Increased acute phase reactant values, constitutional symptoms, neurological symptoms, and treatment with TNFi were independently associated with disease control, while recurrent infections and severe vascular events were the main causes of mortality (10/21 and 6/21, respectively). Conclusion: In patients requiring treatment, symptoms of systemic inflammation and vasculitis and treatment with TNFi are associated with disease control. Recurrent infections and severe vascular events should be treated intensively, as they are the main causes of death. Hematological abnormalities should be monitored, as they decrease the effectiveness of TNFi.

Background: Gorham-Stout syndrome (GSS) is a rare disorder with various presentations and unpredictable prognoses. Previous understandings of GSS mainly focused on progressive bone destruction, while we identified a group of GSS patients with serous effusion as the first symptom. This study aimed to investigate the clinical characteristics of patients with GSS having serous effusion as the first symptom. Methods: Patients diagnosed with GSS were identified through the Peking Union Medical College Hospital Medical Record System. The demographic, clinical, laboratory, and imaging data were collected. Patients who first presented with serous effusion were recruited into the serous group, while those with bone destruction were recruited into the bone group.Results: Of the 23 patients with GSS enrolled, 13 were in the bone group and 10 in the serous group. The median disease duration was shorter and exercise tolerance was lower in the serous group. Despite less frequent bone pain in the serous group, the frequency of bone involvement was similar to that in the bone group. Patients in the serous group had higher rates of bilateral pleural effusion and multiple serous effusion. However, serous effusion also developed with disease progression in the bone group. Of the 17 patients treated with bisphosphonates, 14 reached bone-stable state. However, 5 out of 10 patients with serous effusion still had refractory effusions after bisphosphonates treatment. Three patients received sirolimus treatment, with an improvement in serous effusion. Seventeen patients were followed up; three patients died, two in the bone group and one in the serous group. Conclusions: This study discovered that GSS could first be presented with serous effusion. We believe that this may be a new phenotype of the disease. Sirolimus might help in controlling serous effusion and improving prognosis.

Abstract Background This study aimed to explore the clinical features of gout in adult patients with glycogen storage disease type Ia (GSD Ia). Methods Ninety-five adult patients with GSD Ia admitted to Peking Union Medical College Hospital were retrospectively analysed. A clinical diagnosis of GSD Ia was confirmed in all patients through gene sequencing. All patients had hyperuricaemia; 31 patients complicated with gout were enrolled, and 64 adult GSD Ia patients with asymptomatic hyperuricaemia were selected as a control group during the same period. Clinical characteristics were analysed and compared between the two groups. Results Thirty-one of the 95 patients had complications of gout (median age, 25 years; 11 (35.5%) females). All 31 patients had hepatomegaly, abnormal liver function, fasting hypoglycaemia, hyperuricaemia, hyperlipaemia, and hyperlacticaemia. A protuberant abdomen, growth retardation, recurrent epistaxis, and diarrhoea were the most common clinical manifestations. Among these 31 patients, 10 patients (32.3%) had gout as the presenting manifestation and were diagnosed with GSD Ia at a median time of 5 years (range, 1–14) after the first gout flare. The median age of gout onset was 18 years (range, 10–29). Fifteen of the 31 GSD Ia-related gout patients were complicated with gouty tophi, which has an average incidence time of 2 years after the first gouty flare. The mean value of the maximum serum uric acid (SUA) was 800.5 μmol/L (range, 468–1068). The incidence of gout in adult GSD Ia patients was significantly associated with the initial age of regular treatment with raw corn starch, the proportion of urate-lowering therapy initiated during the asymptomatic hyperuricaemic stage, maximum SUA level, and mean cholesterol level. Conclusions Determination of GSD Ia should be performed for young-onset gout patients with an early occurrence of gouty tophi, especially in patients with hepatomegaly, recurrent hypoglycaemia, or growth retardation. Early detection and long-term regulatory management of hyperuricaemia, in addition to early raw corn starch and lifestyle intervention, should be emphasized for GSD Ia patients in order to maintain good metabolic control. Trial registration Retrospectively registered.

Objective To explore the understanding of refractory gout in Chinese rheumatologists. Methods We conducted an anonymous survey of rheumatologists attending an annual national academic conference on rheumatism. Results Of the 910 rheumatologists who completed the questionnaire, 751 (82.5%) had received relevant continuing medical education (CME). Of these, 140 (18.6%) rheumatologists did not select xanthine oxidase inhibitors as the first treatment for patients with chronic tophaceous gout. Of all respondents, 113 (12.4%), 251 (27.6%) and 324 (35.6%) prescribed incorrect maximum doses of allopurinol, febuxostat and benzbromarone, respectively; this tendency was more pronounced in the non-CME group. Most rheumatologists agreed that complications and comorbidities increased the difficulty of gout management and considered the term refractory gout to describe those cases with uncontrolled symptoms, unmet treatment targets or non-shrinkage of tophi after standardized drug treatment. Moreover, 62.8% (472/751) of specialists considered that a diagnosis of refractory gout was appropriate for patients whose lifestyle and compliance failed to improve despite adequate education and regular urate-lowering therapy. Conclusions Incorrect and inadequate drug therapy may contribute to some cases of refractory gout, especially in physicians without CME. An emphasis on non-drug therapy and the management of comorbidities and complications may reduce cases of refractory gout.

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease caused by ADA2 gene mutation that is characterized by three phenotype domains: vasculopathy and inflammation, hematological abnormality, and immunodeficiency. Most patients are pediatric patients; adult-onset patients are only occasionally reported. To describe a Chinese case of adult-onset DADA2 in a Chinese patient and explore the genotype and phenotype characteristics of adult-onset DADA2. We examined the clinical, serological, and genetic features of a Chinese adult-onset DADA2 patient. English literature on DADA2 was reviewed. The clinical and genetic characteristics of different age and mutation subgroups were compared. A Chinese Han male presented with recurrent fever, rash, immunodeficiency, and significant vascular events since the age of 25 years. Serum ADA2 activity was diminished, and genotyping revealed a unique compound heterozygous mutation of exon2-10del/exon7del in the ADA2 gene leading to complete exon 7 deletion. Treatment with a TNFα inhibitor achieved disease control. A total of 269 cases carrying 102 mutations were analyzed through a literature review. Adult-onset patients had few symptoms in all three clinical domains; vasculopathy and inflammation were the major symptoms. Patients with null mutations had early disease onset and more frequent hematological abnormalities and immunodeficiency. Patients in all subgroups responded well to TNFα inhibitors. We reported the first Chinese adult-onset DADA2 patient, with a unique mutation. Screening for and differentiation of DADA2 are recommended for patients of all ages, as they might become symptomatic later in life and treatment strategies differ from those of traditional vasculitis.

Background: Fever of unknown origin (FUO) is a group of diseases with heterogeneous complex causes that are misdiagnosed or have delayed diagnoses. Previous studies have focused mainly on the statistical analysis and research of the cases. The treatments are very different for the different categories of FUO. Therefore, how to intelligently diagnose FUO into one category is worth studying. Objective: We aimed to fuse all of the medical data together to automatically predict the categories of the causes of FUO among patients using a machine learning method, which could help doctors diagnose FUO more accurately. Methods: In this paper, we innovatively and manually built the FUO intelligent diagnosis (FID) model to help clinicians predict the category of the cause and improve the manual diagnostic precision. First, we classified FUO cases into four categories (infections, immune diseases, tumors, and others) according to the large numbers of different causes and treatment methods. Then, we cleaned the basic information data and clinical laboratory results and structured the electronic medical record (EMR) data using the bidirectional encoder representations from transformers (BERT) model. Next, we extracted the features based on the structured sample data and trained the FID model using LightGBM. Results: Experiments were based on data from 2299 desensitized cases from Peking Union Medical College Hospital. From the extensive experiments, the precision of the FID model was 81.68% for top 1 classification diagnosis and 96.17% for top 2 classification diagnosis, which were superior to the precision of the comparative method. Conclusions: The FID model showed excellent performance in FUO diagnosis and thus would be a potentially useful tool for clinicians to enhance the precision of FUO diagnosis and reduce the rate of misdiagnosis.

Abstract Background Refractory gout is a common problem faced by experienced rheumatologists, relevant research on the difficulties of gout treatment and the understanding of "refractory gout" by rheumatologists is lacking. Methods A total of 910 Chinese rheumatologists attending the annual academic conference on rheumatism completed the electronic questionnaires. The differences in the judgment of refractory gout were analyzed between the senior experience (SE) group and the general experience (GE) group. Results A total of 751 (82.5%) respondents with relevant continuing medical education (CME) were included in our study, including 175 (23.3%) SE rheumatologists and 576 (76.7%) GE rheumatologists. Most of the rheumatologists (715, 95.2%) considered renal function insufficiency as a common complication making gout challenging to treat, while rheumatologists with different experiences had different attitudes towards obesity. For the chronic gouty arthritis patients with one or more tophi, 476 (63.9%) Chinese rheumatologists preferred febuxostat as the first-line treatment option, while 582 (78.3%) chose the maximum daily dose of 80mg for febuxostat, with a higher proportion in SE group than GE group. Meanwhile, the proportion of doctors who chose the dosage of all three uric-lowering drugs consistently with the guidelines was higher in the SE group. Moreover, 123 (70.3%) people in the SE group thought that regardless of the use of drugs for prevention of attack during ULT, the recurrence of symptoms was symptomatic of refractory gout, while fewer in GE group agreed. Similarly, 119 (68.0%) in the SE group thought that failure to achieve the targeted serum uric acid level within 6 months of standardized urate-lowering therapy could be assigned to refractory gout, while fewer in GE group agreed. In terms of personal and social factors, the SE group had a higher percentage of physicians concerned about poor compliance leading to irregular treatment and drug abuse. Conclusions Most of the rheumatologists selected uric-lowering drugs and the maximum dosage of medicines consistently with guidelines. Uncontrolled symptoms, unattainable therapeutic targets, and unimproved lifestyle and compliance of patients are difficulties that Chinese rheumatologists have to face with during gout treatment.

>一、背景2004年,本研究团队与美国风湿病学会前主席Schumacher教授合作开展了对中国内科医生有关痛风诊治知识的问卷调查 [1] 。2006年北京协和医院在国内率先设立痛风专科门诊 [2] 。2010年起参与了美国风湿病学会（ACR）/欧洲抗风湿病联盟（EULAR）主持的多中心研究"关于痛风发作评定标准的临床验证研究" [3-4] ,为全球痛风协作组的唯一中国单位。2005年以来,我们一直参与社区居

通过1例以活动后胸闷为主要临床表现的酒精性心肌病患者的临床讨论,分析对于该类患者的全科管理理念以及良好生活习惯的重要意义.

通过一例以Purtscher样视网膜病变为首发表现的自身免疫性血栓性血小板减少性紫癜案例，分析Purtscher样视网膜病变在其诊治中的意义。

报道1例以肥大性骨关节病为首要表现的肺癌。患者临床表现、四肢骨X线片、全身骨显像符合肥大性骨关节病的表现，继发病因筛查发现右肺占位，最终病理学检查明确诊断肺腺癌。

The objective of this article is to investigate the clinical features of intestinal pseudo-obstruction (IPO) and/or ureterohydronephrosis in systemic lupus erythematosus (SLE). Sixty-one SLE patients with IPO and/or ureterohydronephrosis were analyzed retrospectively. A total of 183 cases were randomly selected as controls from 3840 SLE inpatients without IPO and ureterohydronephrosis during the same period. Patients were assigned to 1 of the 3 groups (SLE with IPO and ureterohydronephrosis, SLE with IPO, and SLE with ureterohydronephrosis). The clinical characteristics, treatments, and prognosis were compared between the 3 groups. There were 57 females and 4 males, with a mean age of 32.0 years. IPO was the initial manifestation of SLE in 49.1% of the cases, whereas ureterohydronephrosis in 32.5%. All patients were initially treated with a high-dose steroid. Thirty-one of these patients (50.8%) also received intravenous methylprednisolone pulse therapy. Two patients died of bowel perforation and lupus encephalopathy, and the other 59 patients (96.7%) achieved remission after treatment. The incidences of fever, glomerulonephritis, nervous system involvement, serositis, erythrocyte sedimentation rate elevation, hypoalbuminemia, hypocomplementemia, and anti-SSA antibody positivity were significantly higher in patients with IPO and/or ureterohydronephrosis than in the control group (without IPO and ureterohydronephrosis). Also, patients with IPO and/or ureterohydronephrosis had higher SLE Disease Activity Index scores than control patients. Compared with SLE patients with IPO, the patients with IPO and ureterohydronephrosis had a significantly higher incidence of gallbladder wall thickening, biliary tract dilatation, and serositis, whereas the patients with ureterohydronephrosis had less mucocutaneous involvement and serositis. Eight of the 47 IPO patients who initially responded well to immunotherapy relapsed; however, all responded well to retreatment with adequate immunotherapy. Of these 8 patients, 4 relapsed following poor compliance and self-discontinuation of steroid or immunosuppressant therapy. The rate of poor compliance with immunotherapy and the number of organ systems involved in patients in the recurrent IPO group were significantly higher than those in the nonrecurrent IPO group. IPO and ureterohydronephrosis are severe complications of SLE. As patients usually respond readily to early optimal steroid treatment, early diagnosis and timely initiation of glucocorticoid are important to relieve symptoms, prevent complications, and improve prognosis.

OBJECTIVE:Based on 2006 revised classification criteria of definite antiphospholipid syndrome (APS) and definition of new APS subsets, we investigated clinical features of APS patients, correlation between thrombotic events and related antibodies was assessed as well. METHODS:165 patients with APS were enrolled and analysed retrospectively. RESULTS:124 female and 41 male patients were included. 116 cases (70.3%), 34 cases (20.6%), 10 cases (6.1%), and 5 cases (3.0%) were classified as definite APS, probable APS, seronegative APS, and microangiopathic APS (MAPS) respectively. Among 124 patients accompanied with other diseases, 113 (91.1%) were autoimmune diseases, mostly systemic lupus erythematosus (79.6%). 121 (73.3%) patients had episodes of thrombosis, with majority of deep vein thrombosis. The patients with positive test of lupus anticoagulant (LA) only were more likely to have episodes of thrombosis than with positive anticardiolipid antibody (ACL) only (86.0% versus 55.7%; P < 0.05). Among 61 patients with prolonged APTT, the presence of LA was detected in 50 (82.0%) patients, and ACL in 34 (55.7%) patients. CONCLUSION:APS patients could be classified into several subgroups according to their clinical features. Venous thromboses are more common than arterial thromboses, and positive of LA correlates thrombosis more than ACL.