Immune checkpoint inhibitor-induced eosinophilic fasciitis: a case report and literature review / 中华内科杂志

A 58-year-old male patient with angioimmunoblastic T-cell lymphoma developed a rash and skin tightness on the face, limbs, and trunk together with joint stiffness and dysfunction after 6 months of treatment with the programmed cell death protein-1 inhibitor camrelizumab. Laboratory tests revealed progressive eosinophilia over 6 months, with the eosinophil count increasing from 0.07×10 9/L to 3.3×10 9/L. Magnetic resonance imaging showed thickened skin of both forearms, while T 2-weighted imaging showed markedly increased signal intensity within the myofascia. Skin biopsy of the right forearm showed thickened and fibrosed fascia and infiltration of inflammatory cells, including lymphocytes, plasma cells, and eosinophils. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced eosinophilic fasciitis (EF). After beginning treatment with methylprednisolone (40 mg daily), methotrexate (10 mg/week), and baricitinib (4 mg daily), his symptoms of skin tightness and joint dysfunction significantly improved within 1 month, and his peripheral blood eosinophil count decreased to 0.17×10 9/L. ICI-induced EF is a rare immune-related adverse reaction. To date, only 20 cases have been reported in published foreign literature, and their clinical characteristics are summarized here. The time from ICI treatment to EF was 12 (8,15) months, and the main clinical manifestations included skin involvement ( n=19), joint dysfunction ( n=11), myalgia/muscle weakness ( n=9), and peripheral eosinophilia ( n=16). After treatment, the clinical symptoms of EF improved in 17 patients, and eosinophil counts returned to normal after 3 (1,8) months. EF is a dysfunctional adverse response to ICI therapy. Tumor patients undergoing immunotherapy should be monitored for symptoms of EF. Early treatment is essential for preventing complications.

The characteristics and associated factors of functional limitation in patients with rheumatoid arthritis / 中华内科杂志

Objective:To investigate the characteristics of functional limitation and associated factors in patients with rheumatoid arthritis (RA).Methods:Consecutive patients with RA were recruited from August 2015 to June 2019 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. Demographic and clinical characteristics including age, gender, erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) of pain, clinical disease activity index (CDAI), modified total Sharp score were collected. Physical function was assessed by the Stanford health assessment questionnaire disability index (HAQ-DI).Ordered logistic regression was used to analyze the related factors of HAQ-DI.Results:A total of 643 RA patients were finally recruited including 114 males and 529 females with mean age (49.7±12.9) years. There were 399 (62.1%) patients having different degrees of functional limitation, who were classified as mild (293, 45.6%), moderate (73, 11.4%) and severe (33, 5.1%). The prevalence of functional limitation was positively correlated with age and disease activity. The most restricted activity was walking [43.5% (280/643)], followed by gripping [36.1% (232/643)], reaching [35.5% (228/643)], daily activities [33.4% (215/643)], hygiene [33.0% (212/643)], dressing and grooming [29.7% (191/643)] and arising [29.1% (187/643)], and the last eating [18.4% (118/643)]. Multivariate ordered logistic regression analysis showed that age ( OR=1.019, 95% CI 1.004-1.035),pain VAS ( OR=1.820, 95% CI 1.616-2.050), ESR ( OR=1.009, 95% CI 1.001-1.017), CDAI ( OR=1.080, 95% CI 1.059-1.102) and modified total Sharp score ( OR=1.010, 95% CI 1.004-1.015) were associated factors of functional limitation. Conclusion:The majority RA patients have functional limitation. Age, pain and active disease are independent associated factors. Therefore, target treatment and control of pain should be emphasized in RA patients.

The prevalence of hypertension and its associated factors in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective:To investigate the prevalence of hypertension and its associated factors in rheumatoid arthritis (RA) patients.Methods:Consecutive Chinese patients with RA were recruited from August 2015 to September 2019 at Department of Rheumatology, Sun Yat-sen Memorial Hospital. Demo-graphic data and clinical data were collected including indicators of disease activity, functional assessment and radiographic assessment, comorbidities and previous medications. Logistic regression analysis was used to evaluate the related factors of hypertension in RA patients.Results:There were 674 RA patients recruited with 82.3%(555/674) female and mean age (50±13) years. The prevalence rate of hypertension was 32.9% (222/674), followed by dyslipidemia (9.9%, n=67), type 2 diabetes (8.8%, n=59), hyperuricemia (8.5%, n=43), fatty liver disease (8.0%, n=54), cardiovascular disease (6.2%, n=42) and chronic kidney disease (3.3%, n=22). Compared with those without hypertension, RA patients with hypertension had advanced age with longstanding disease duration, higher disease activity indicators, worse joint destruction, and higher proportions of comorbidities. Multivariate logistic regression analysis showed that comorbidities including hyperuricemia [ OR=1.977, 95% CI(1.002, 3.900)], dyslipidemia [ OR=1.903, 95% CI(1.102, 3.288)] and fatty liver disease [ OR=2.335, 95% CI(1.278, 4.265)] were risk factors of hypertension after adjustment for age and gender. Conclusion:Hyperten-sion is the most common comorbidity in RA patients which is associated with comor-bidities including hyperuricemia, dyslipidemia and fatty liver disease. Detection and management of hyperten-sion and other cardiovascular disease related comorbidities in RA patients should be emphasized.

Rosiglitazone inhibits osteoclastogenesis in rheumatoid arthritis by down-regulating RANKL expression and suppressing ERK phosphorylation / 中国病理生理杂志

AIM: To investigate the effects of rosiglitazone on fibroblast-like synoviocyte ( FLS )-induced osteoclastogenesis in rheumatoid arthritis ( RA) and the related mechanism.METHODS: RA-FLS were cocultured with peripheral blood monocytes from healthy volunteers in the presence of macrophage colony-stimulating factor ( M-CSF) and rosiglitazone.Osteoclasts were assayed by tartrate-resistant acid phosphatase ( TRAP) staining.Resorption lacunae area was identified by toluidine blue staining and quantified by image analysis software.The mRNA expression of RANKL and OPG was evaluated by real-time PCR, and the protein levels of RANKL, OPG, p-ERK, p-p38 and p-JNK were measured by Western blot.RESULTS:Compared with control group ( without rosiglitazone treatment) , rosiglitazone at concentration of 15 μmol/L significantly decreased the number of osteoclasts (P0.05 ) . CONCLUSION:Rosiglitazone inhibits RA-FLS-induced osteoclast formation and its resorption activity by down-regulating RANKL expression and ERK phosphorylation, suggesting that rosiglitazone may inhibit RA osteoclastogenesis and bone re-sorption.

Efficacy of tocilizumab on disease activity and psychological state in patients with refractory rheumatoid arthritis / 中华风湿病学杂志

Objective To observe the efficacy and safety of tocilizumab on patients with refractory rheumatoid arthritis (RA).Methods Eighteen RA patients who were refractory to disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor-α (TNF-α) antagonist were treated with tocilizumab were included into this study.Their clinical disease activity indices,Hospital Anxiety and Depression Scale (HADS)and safety were evaluated regularly.Statistical analysis was conducted with Mann-Whitney U test and x2 test.Results According to clinical disease activity index,44％(8/18) of patients reached treatment target 2 weeks after the first infusion of tocilizumab,and 78％ (14/18) reached treatment target after three infusions of tocilizumab.Fifty-six percent (10/18) of patients had anxiety and 22％ (4/18) had depressive symptoms at baseline.After three infusions of tocilizumab,6％(1/18) had anxiety symptoms and 11％(2/18) had depressive symptoms.The adverse effects included upper respiratory tract infection,aminotransferase elevation and neutropenia (3 patients,respectively).Conclusion Tocilizumab can rapidly and significantly improve the disease activity and psychological state with good tolerance and safety,which can be applied to Chinese refractory RA patients who failed with DMARDs or TNF-α antagonist.

Survey on doctor's screening practice and clinical management for hepatitis B virus infection in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate doctor's screening practice for hepatitis B virus (HBV) infection before immunosuppressive therapy for rheumatoid arthritis (RA) patients and clinical management of RA patients with positive surface antigen of HBV (HBsAg).Methods One hundred fifty doctors who treated RA patients in daily clinic were survied with a modified American College of Rheumatology (ACR) questionnaire which was composed of demographic data and 10 multiple-choice questions.Step-forward logistic regression analysis was performed to find out the influencing factors,then receiver operator characteristic curve analysis and area under the curve were performed to confirm the influencing factors.Results One hundred and thirtytwo effective questionnaires were collected.Before immunosuppressive therapy,HBV screening rate in outpatients with RA was significandy lower than that in hospitalized patients (68.7％ vs 94.6％,x2=31.5,P＜0.01).Only 23.7％(31/131) of doctors considered antiviral treatment for all RA patients with positive HBsAg.One hundred and thirteen doctors had clinical experience of antiviral treatment,but only 30.1％(34/113) and 23.9％ (27/113) of these doctors chose entecavir or adefovir as the antiviral drug respectively,59.3％ (67/113) prescribed antiviral drug before or together with immunosuppressive therapy compared with 40.7％(46/113) after HBV reactivation.Only 20.4％(23/113) of doctors would sustain antiviral treatment until the termination of steroid or disease modifying antirheumatic drugs (DMARDs).During immunosuppressive therapy for HBsAg(+) RA patients,11.4％(15/132) and 30.3％(40/132) of doctors reported no regular monitoring of aminotransferase or HBV DNA respectively.Conclusion Our survey shows that HBV screening rate in outpatients with RA is low and low awareness of antiviral treatment for all RA patients with positive HBsAg,and lack of awareness of indication,choosing of antiviral drugs,initiation,monitoring and duration of antiviral treatment during immunosuppressive therapy.Further medical education on the associated information and importance to collaborate with hepatologists should be emphasized.

Liver safety of tumor necrosis factor-α antagonists in inflammatory arthropathy patients with concurrent chronic hepatitis B infection: a prospective observation / 中华风湿病学杂志

Objective To investigate the effect of tumor necrosis factor (TNF)-α antagonists on liver function and reactivation of hepatitis B virus ( HBV ) in patients with inflammatory arthropathy with concurrent chronic HBV infection.Methods Patients with active rheumatoid arthritis (RA) and ankylosing spondylitis (AS) who were grouped according to serum HBV biomarkers were treated with TNF-α antagonist.The liver function and reactivation of HBV were monitored before and after anti-TNF-α therapy.Kruskal-Wallis one-way analysis of variance on ranks of continuous variables and x2 test or Fisher's exact test for categorical variables among 3 or more groups.Results Fifty patients were enrolled with 3 to 23 months of follow-up visit.The level of transaminases in chronic HBV infection group [n=11,AST (36±18) U/L,ALT (44±46) U/L] were significantly higher than that in past HBV exposure group [n=16,AST (22±6) U/L,ALT (17±9) U/L] or free of HBV infection group [n=23,AST (19±6) U/L,ALT (15±9) U/L](AST:x2=11.161,P＜0.01,ALT:x2=8.038,P＜0.01).One patient with elevated baseline HBV-DNA load was treated concomitantly with lamivudine and anti-TNF-α therapy,and the HBV-DNA load reduced about to normal 4 months later.Among the other 10 patients with normal baseline HBV-DNA load in chronic HBV infection group,one patient showed reactivation of HBV with elevated transaminases after anti-TNF-α therapy; another patient had only elevated transaminases without reactivation of HBV,and the transaminases returned to normal after withdrawal of antiTNF-α therapy,which suggested drug-induced liver injury.All patients in both past HBV exposure group and free of HBV infection group remained HBsAg negative after the therapy.Conclusion Patients with inflammatory arthropathy should be screened for HBV infection and check liver function before anti-TNF-α therapy,and carefully monitor the reactivation of HBV and liver function during treatment.Patients with concurrent chronic HBV infection should be treated conco-mitantly with anti-virus and anti-TNF-α therapy if they have elevated baseline HBV-DNA load (＞105 copies/ml,in particular) and good economic situation.