Effect of leflunomide on the peripheral nerves in rheumatoid arthritis

Background: The objective of this study was to determine the neurophysiological effects of leflunomide on peripheral nerves in rheumatoid arthritis. Methods: We conducted a prospective cohort trial of 32 patients with rheumatoid arthritis with 16 patients receiving leflunomide treatment and 16 receiving other disease‐modifying anti‐rheumatic drug therapies. Clinical, laboratory and neurophysiological measurements were used to determine the presence of a peripheral neuropathy in these patients at study entry and then after a further 3 and 6 months. Results: Fifty‐four per cent of the leflunomide group and 8% of the control group had an increase in their neuropathy symptom score 6 months into the study (P = 0.01). No correlation was found between the electrophysiological findings and the clinical symptoms. There was no significant difference between the two groups in upper and lower limb sensory and motor amplitudes and conduction velocities recorded at 3 and 6 months. One patient developed both clinical and neurophysiological evidence of a peripheral neuropathy 5 months into the study that improved after cessation of leflunomide therapy and cholestyramine washout. Conclusion: After 6 months of exposure we found that leflunomide was associated with an apparent increase in the clinical symptoms of peripheral neuropathy in patients with rheumatoid arthritis. These symptoms did not correlate with neurophysiological studies.     

类风湿关节炎并发周围神经病变46例临床特点分析

目的:通过分析46例类风湿关节炎（RA）并发周围神经病变（PN）患者的临床特点,旨在提高临床医生对其的认识水平。方法:选2012年9月至2019年9月郑州大学第一附属医院风湿免疫科RA并发PN者46例,按1∶2匹配92例RA患者,分析其临床资料、辅助检查、治疗方案及随访。采用受试者操作特征（ROC）曲线评估类风湿因子（...     

Suppression of autoantibodies to factor VIII and correction of factor VIII deficiency with a combined steroid-cyclophosphamide-porcine factor VIII treatment in a patient with rheumatoid arthritis.

The presence of autoantibodies against factor VIII is an unusual but serious complication in rheumatoid arthritis. We describe the case of a patient who developed this kind of complication, with spontaneous bleeding and marked changes in the haematological parameters, that was unsuccessfully treated with a high dose of intravenous gammaglobulin. Subsequently, combined therapy with porcine factor VIII concentrate, cyclophosphamide and steroids led to the disappearance of the anti-factor VIII autoantibodies.     

Managing comorbidity in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease that decreases physical function and imposes substantial medical costs. Comorbid conditions are common in patients with RA and they adversely affect quality of life and RA‐related outcomes such as work disability and mortality. Rheumatologists have the important responsibility to consider comorbidities and their risks when treating patients and to adapt therapies to the specific situation of individual patients. This paper discusses the common comorbidities in patients with RA and management approaches.     

A case of peripheral neuropathy and skin ulcer in a patient with rheumatoid arthritis after a single infusion of tocilizumab

We report a case of peripheral neuropathy and skin ulcer in a patient with rheumatoid arthritis (RA) who received tocilizumab. A 65-year-old woman with a 20-year history of RA participated in a tocilizumab clinical trial. She received a single dose of 8 mg/kg tocilizumab intravenously. The following day the patient started to experience numbness and purpura in all four extremities. The purpura of her left lower limb became necrotic, and a skin ulcer appeared 3 weeks later. Steroid-pulse treatment was initiated 12 weeks after tocilizumab administration, with the result that the numbness improved, and the skin ulcers showed complete epithelialization.     

Cardiac involvement in patients with rheumatoid arthritis

Background and aim: In rheumatoid arthritis (RA), although the target organ is the synovium, extra‐articular involvement is also seen. All layers of the heart can be inflamed and pericarditis is the most common type of involvement. The frequency of cardiac involvement in patients with RA and its relation with other patient characteristics were analysed in this study. Methods: One hundred patients with RA were included in the study. Patients were evaluated in terms of their sex, age, disease duration, activity of the disease and history of previous heart disease. Electrocardiography (ECG) and echocardiography were performed. The cardiac abnormalities, laboratory parameters, disease duration and the age of the patient were separately compared. Student t‐test was used for these comparisons and P < 0.05 was accepted to be statistically significant. Results: Ages of the patients, 15 of whom were male and 85 were female, varied between 19 and 78 years (mean 50.5 ± 12.7 years). 23% of the patients were RF‐negative and 77% were RF‐positive. The distribution of the patients according to the Steinbrocker's functional classification was as follows: 16 patients (16%) Class I, 55 patients (55%) Class II, 23 patients (23%) Class III and 5 patients (5%) Class IV. ECG abnormalities were found in 7 patients (7%). Echocardiographic abnormality was detected in 67 of the 100 patients (67%) with minimal pericardial effusion in 15 patients (15%), mitral valvular involvement in 26 patients (26%), aortic valve involvement in 24 patients (24%), ascendant aorta dilatation in 7 patients (7%) and diastolic dysfunction in 57 patients (57%). Conclusions: Cardiovascular system involvement which is an extra‐articular involvement of RA is asymptomatic in most of the patients. Thus, we believe that by a periodical thorough evaluation of patients and aggressive treatment for identified problems can significantly reduce cardiovascular morbidity and mortality in patients with RA.     

Effectiveness and safety of rituximab in special types of rheumatoid arthritis

Objectives

To elucidate the efficacy and safety of rituximab in special types of rheumatoid arthritis.

Methods

We retrospectively reviewed all patients with rheumatoid arthritis with lymphoproliferative disorder or vasculitis treated with rituximab between April 2010 and June 2022 at Keio University Hospital. We assessed the effectiveness of rituximab using the Disease Activity Score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and safety of rituximab during the disease course. We also assessed the glucocorticoid-sparing effects of rituximab.

Results

We included eight patients with a history of lymphoproliferative disorder and five patients with rheumatoid vasculitis. They were treated with rituximab without high-dose glucocorticoid. The mean DAS28-ESR and CDAI scores significantly improved 12 months after rituximab administration (DAS28-ESR, 4.7 vs. 2.7, p < .001; CDAI, 16.0 vs. 5.1, p = .006, respectively), and the dose of prednisolone was reduced from a mean of 7.4 mg/day to 4.0 mg/day at 12 months (p = .05) and 3.2 mg/day at the last visit (p = .04). During the mean follow-up period of 52 months, we recorded one recurrence of lymphoproliferative disorder (not B-cell type) in patients with a history of lymphoproliferative disorder and remarkable improvement of skin ulcers in patients with vasculitis.

Conclusion

B-cell depletion by rituximab may be a useful treatment option for patients with lymphoproliferative disorder and rheumatoid vasculitis.     

Analysis of T cell receptor V alpha polymorphisms in rheumatoid arthritis

OBJECTIVE—To test for association of T cell receptor (TCR) V alpha polymorphisms and rheumatoid arthritis (RA) in British and Swiss white populations.
METHODS—TCRAV polymorphisms were analysed in RA patients and controls by single strand conformational polymorphism (SSCP) analysis. Associations were sought between defined genotypes and RA, and the effect of HLA-DR4 status analysed. Putative associations were then retested further in new groups of patients and controls. Overall, 360 RA patients and 197 controls were studied.
RESULTS—No association between TCRAV5S1, V6S1, V8S1, V17S1 or V21S1 polymorphisms and RA were observed in the initial population screened. Stratification for DR4 status showed an increase of V5S1*01/*01 in DR4 positive versus DR4 negative patients (χ² = 7.19, p=0.028 (2df), p=0.14 after correction for multiple comparisons). This putative association was tested in three further patient groups, none of which showed significant increase of V5S1*01/*01 in DR4 positive patients, although an overall trend towards an increase in V5S1*01/*01 was observed.
CONCLUSION—No evidence was found for a strong association of TCRAV genes and RA in a white population. However, these results suggest a weak association of V5S1*01/*01 with DR4 positive RA, although this requires confirmation using larger groups of patients and controls.

Keywords: rheumatoid arthritis; immunogenetics; T cell receptor     

Familial rheumatoid arthritis in patients referred to rheumatology clinics of Tabriz, Iran

Background: The familial clustering of rheumatoid arthritis (RA) in first and second degree relatives of patients supports the role of genetic factors. The proportion of heredity in its development is roughly 60%; however, most individuals closely related to someone with RA do not get the disease. Considering the lack of sufficient data on the familial aggregation of RA in Iran, we designed this study for clarifying the familial prevalence of RA. Objective: To determine the prevalence of RA among relatives of patients with RA and to evaluate the mean disease onset age in relatives. Methods: In a longitudinal study from July 2008 to July 2010, we followed 210 unrelated patients with RA and their first and second degree relatives (FDR+ and SDR+), by interviewing and physical examination of those with symptoms, to ascertain prevalence. Familial RA was defined by presence of at least two siblings fulfilling the 1987 ACR criteria for RA. Results: We demonstrated that 17.6% of patients have at least one affected relative. The prevalence of RA in the family of studied patients was 0.83% (42 people). Thirty‐two in FDR+ and 10 people in SDR+ (2.53% and 0.26% of all family), also 1.12% in female relatives and 0.39% in male relatives had RA. The odds ratio for FDR/SDR was 2.52. The mean age at disease onset in relatives was 42.30 ± 1.51 years in FDR+ and 34.40 ± 2.10 years in the SDR+ group (0.03). Conclusion: The risk of RA is greatest in FDR+ and is likely to be due to a combination of inherited and environmental factors.     

Composition and function of peripheral blood stem and progenitor cell harvests from patients with severe active rheumatoid arthritis

High-dose chemotherapy with autologous stem cell rescue has been proposed as an intensive therapy for severe rheumatoid arthritis (RA). In view of previous observations of abnormal haemopoiesis in RA patients, the composition and function of peripheral blood stem cell harvests (PBSCH) was investigated. Compared with PBSCH from healthy allogeneic donors mobilized with the same dose of G-CSF (filgrastim; 10 μg/kg/d, n = 14), RA PBSCH (n = 9) contained significantly fewer mononuclear cells (375 v 569 × 10⁶/kg, P = 0.03) and CD34⁺ cells (2.7 v 5.8 × 10⁶/kg, P = 0.003). However, there were increased proportions of CD14⁺ cells (P = 0.006) and CD14⁺CD15⁺ cells (the phenotype of previously described ‘abnormal’ myeloid cells, P = 0.002) in the RA PBSCH which translated into 3.5- and 7-fold increases respectively on a per CD34⁺ cell basis. There were no differences in T-cell activation status as judged by proportions of CD4⁺ and CD8⁺ expressing CD45RA, CD45RO, HLA-DR and CD28 (RA PBSCH, n = 7, donor PBSCH, n = 5, P = 0.2–0.7). Phytohaemagglutinin responses determined fluorocytometrically with induction of CD69 expression were reduced in CD4⁺ and CD8⁺ cells following filgrastim administration in 3/3 RA patients tested. Compared with bone marrow as a potential source of CD34⁺ cells, PBSCH contained 11-fold more T cells (P < 0.0005), 8-fold more B cells (P < 0.0005) and 4-fold more monocytes (P = 0.02). In short-term methylcellulose culture there were no differences in colony counts (CFU-GM, CFU-GEMM, BFU-E) per CD34⁺ cell from PBSCH from RA patients (n = 11) and healthy donors (n = 10). Long-term culture initiator cells were cultured successfully from cryopreserved PBSCH from RA patients (n = 9). In conclusion, PBSCH from RA patients differed significantly in composition from normal individuals, but in vitro studies support normal stem and progenitor cell function. Changes in T-cell function occur during mobilization in RA patients. This work provides reassurance for the use of PBSCH as haematological rescue and baseline data for clinical trials of graft manipulation strategies in patients with RA.     

Clinical and psychosocial factors associated with depression and anxiety in Singaporean patients with rheumatoid arthritis

Aim: To assess the frequency of, and factors associated with, depression and anxiety in Singaporean patients with rheumatoid arthritis (RA). Method: One hundred RA patients were recruited in a cross‐sectional study. Socio‐demographics, severity of anxiety and depression, disease activity, levels of serological markers and health‐related quality of life were analyzed. Results: Twenty‐six percent presented with anxiety, 15% with depression and 11% with both. Univariate regression showed that age (P = 0.039), Disease Activity Scale (DAS‐28) (P < 0.001), number of medications (P < 0.001) and rheumatoid factor (RF) (P < 0.001) were positively associated with severity of depression, while income (P = 0.001), education (P = 0.029), self‐perceived social support (P = 0.007), Short form 12 (SF‐12) physical health (P < 0.001) and SF‐12 mental health (P < 0.001) were negatively associated with severity of depression. After adjustment for confounding factors in multivariate regression, income (β = ?0.347, P = 0.018), RF (β = 0.304, P = 0.043) and SF‐12 mental health (β = ?0.501 P = 0.001) remained significantly associated with depression. Univariate regression showed that DAS‐28 (P = 0.009), number of medications (P = 0.004) and RF (P = 0.043) were positively associated with anxiety, while income (P = 0.022), self‐perceived social support (P = 0.04), SF‐12 physical health (P < 0.001) and SF‐12 mental health (P < 0.001) were negatively associated with anxiety. After adjustment for confounding factors, no factors remained significantly associated with anxiety. Conclusion: Low income, high levels of RF and poor mental health were associated with depression in RA. Our findings may help to formulate depression screening strategies. Further research is required to identify the role of RF in depression.     

Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis,assessment and management

Painful diabetic peripheral neuropathy (DPN) is common, is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician. Although poor glucose control and cardiovascular risk factors have been proven to contribute to the aetiology of DPN, risk factors specific for painful DPN remain unknown. A number of instruments have been tested to assess the character, intensity and impact of painful DPN on quality of life, activities of daily living and mood. Management of the patient with DPN must be tailored to individual requirements, taking into consideration the co‐morbidities and other factors. Pharmacological agents with proven efficacy for painful DPN include tricyclic anti‐depressants, the selective serotonin and noradrenaline re‐uptake inhibitors, anti‐convulsants, opiates, membrane stabilizers, the anti‐oxidant alpha‐lipoic acid and topical agents including capsaicin. Current first‐line therapies for painful DPN include tricyclic anti‐depressants, the serotonin and noradrenaline re‐uptake inhibitor duloxetine and the anti‐convulsants pregabalin and gabapentin. When prescribing any of these agents, other co‐morbidities and costs must be taken into account. Second‐line approaches include the use of opiates such as synthetic opioid tramadol, morphine and oxycodone‐controlled release. There is a limited literature with regard to combination treatment. In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated. There are a number of unmet needs in the therapeutic management of painful DPN. These include the need for randomized controlled trials with active comparators and data on the long‐term efficacy of agents used, as most trials have lasted for less than 6 months. Finally, there is a need for appropriately designed studies to investigate non‐pharmacological approaches. Copyright © 2011 John Wiley & Sons, Ltd.     

Osteonecrosis and monoarticular rheumatoid arthritis treated with intra-articular adalimumab

Abstract

We report a 54-year-old patient with RA presented with osteonecrosis (ON) and monoarthritis of left knee remitting in the last 2 years. Monoarthritis was resistant to disease-modifying antirheumatic drugs (DMARDs) and intra-articular corticosteroids. Intra-articular administration of adalimumab provided a good clinical and radiographic response. Synovitis resolved and osteonecrosis disappeared almost totally.     

血清胆红素与糖尿病周围神经病变相关性研究

目的探讨血清胆红素与糖尿病周围神经病变（DPN）的关系。方法收集110例2型糖尿病（T2DM）并发周围神经病变患者（DPN组）、220例单纯T2DM患者（DM组）和健康体检者278名（Con组）的血清胆红素等临床资料,并进行Logistic回归分析,筛选DPN的危险因素。对间接胆红素（IBIL）进行进一步的分析。结果（1）低血清INL、病程长、LDLC升高是DPN的危险因素。（2）协方差分析表明,控制尿白蛋白（UA1b）等因素后,DPN组的INL水平[（9．7±0．6）μmol／L]仍然明显低于DM组[（12．0±0．6）μmol／L]和Con组[（11．4±0．3）μmol／L]。结论低血清IBIL与DPN密切相关,是DPN发病相关因素之一。