Cerebral Tuberculosis in a Patient Following Treatment With Infliximab for Ankylosing Spondylitis: A Case Report.

Ankylosing spondylitis (AS) mainly belongs to the group of axial spondylitis. It is a chronic inflammatory disease that primarily affects the spine, but can also affect peripheral joints. It is characterized by inflammatory lower back pain and morning stiffness. Tuberculosis is still a cause of morbidity and mortality in developing countries. Management of patients with AS consists of patient education, spinal mobility exercises, non-steroidal anti-inflammatory drugs (NSAIDs), corticotherapy, and anti-tumor necrosis factor alpha (TNF-α) biological agents. Anti-TNF-α biological agents have changed the prognosis of patients with AS. They contain anti-TNF-α monoclonal antibodies (golimumab, infliximab, adalimumab, certolizumab) and the soluble TNF-α receptor (etanercept). Hip and knee involvement is common in patients with AS, as evidenced in radiographs as bone erosion and joint space narrowing. The patient may have severe pain, stiffness, and loss of mobility, and the treatment involves surgery for joint arthroplasty. We present the case of a 63-year-old patient with axial spondyloarthritis who was treated with infliximab and developed cerebral tuberculosis after three years of biological therapy. The purpose of the study is to determine the possibility of resuming biological therapy at the time of AS reactivation, given the long-term treatment and adverse reactions of cortisone therapy (aseptic necrosis of the femoral head).

Rheumatological Adverse Events Following Immunotherapy for Cancer.

Background and Objectives: The occurrence of rheumatological side effects in a patient after receiving immunotherapy for cancer is becoming increasingly common. Oncologists often fail to diagnose and refer affected patients to rheumatologists. This paper presents the various rheumatological adverse events that occur after immunotherapy in patients as well as their treatment and evolution. Materials and Methods: A total of 36 patients were monitored between November 2018 and March 2020. The oncologist monitoring the immunotherapy-treated patients identified the occurrence of musculoskeletal side effects. The grading of toxicities was performed by both the oncologist and the rheumatologist using common terminology criteria for adverse events (CTCAE). Rheumatological treatment was administered, and for some patients, immunotherapy was discontinued. Results: The clinical presentations of the patients varied. Mild side effects (grade 1-2) were reported in a higher proportion than severe side effects (grade 3-5). Therefore, thirty-one patients had mild-to-moderate side effects, and five patients had severe side effects. Adverse reactions occurred, on average, 10 weeks after the initiation of immunotherapy; this indicated that the severity of the toxicity was dose dependent. Patients were treated with NSAIDs or prednisone, depending on the severity of the side effects, and for patients with severe manifestations, immunotherapy was discontinued. The remission of rheumatic manifestations varied depending on the grade of the manifestations. Conclusions: The clinical, biological, and ultrasound presentations of the patients with adverse events followed by cancer treatments differed from classic rheumatological manifestations. Thorough examinations of these patients by both oncologists and rheumatologists are needed in order to correctly diagnose and treat rheumatological adverse events. Multiple studies that include a larger number of participants are needed in order to better understand the pathogenesis and clinical evolution of these patients under different treatment conditions.

Musculoskeletal adverse reactions after immunotherapy for cancer: A case series.

Immunotherapy has revolutionized cancer treatment. Immune checkpoint inhibitors (ICIs) including antibodies targeting cytotoxic T lymphocyte associated antigen-4 and programmed cell death 1 have been shown to be effective in the treatment of certain types of cancer. The benefit of these therapies is to prolong life expectancy in the case of metastatic malignancies. Rheumatic adverse events are not very common. In the present study, 9 patients were monitored between November 2018 and January 2020. The oncologist, who identified the occurrence of rheumatic toxicities after the treatment with ICIs, evaluated the patients. Only oncological patients with rheumatic manifestations after the start of immunotherapy were included. Toxicity grading was performed by both the oncologist and the rheumatologist, on a scale from 1 to 5 (1, mild; 2, moderate; 3, severe; 4, life-threatening; 5, death related to toxicity). The results showed that rheumatoid factor, which was sampled in each patient, was negative in all cases. Patients were treated with nonsteroidal anti-inflammatory drugs or prednisone depending on the severity of the adverse events. The results varied with the severity of the adverse events. In conclusion, as the number of patients treated with ICIs increases, so will the number of patients presenting with immune-related adverse events (irAEs). The collaboration between oncologists and rheumatologists should be intimate to provide optimal treatment to patients. Musculoskeletal manifestations secondary to ICIs are slightly different from other rheumatologically conditions making diagnosis, treatment and monitoring difficult. Thus, irAEs are new and challenging for oncologists, thus understanding of the pathogenesis and clinical characteristics must be improved for better treatment guidelines.

Risk of active tuberculosis in patients with inflammatory arthritis receiving TNF inhibitors: a look beyond the baseline tuberculosis screening protocol.

Tuberculosis (TB) is a major concern in patients receiving TNF inhibitors (TNFi). This study aimed to assess the incidence of active TB and the efficacy of TB prevention measures used over the years, and to determine risk factors for developing TB, in a single-centre cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) receiving TNFi. Data of all patients in whom treatment with TNFi was initiated in our rheumatology clinic until December 1st 2014 have been retrospectively analysed. The cohort was divided into 3 groups per the mandatory LTBI screening method at baseline: tuberculin skin test (TST) with a positive threshold of either 10 mm (group TST1), or 5 mm (group TST2), and QuantiFERON®-TB Gold test (group QFT). The incidence of active TB was analysed for each group and compared to TB incidence data in general population. Five hundred fifty patients were included (305 RA, 42 PsA, 203 AS); 97 patients belonged to the TST1, 229 to the TST2 and 224 to the QFT group. The number of active TB cases/time of exposure to TNFi (person-years, PY) was 8/593.5, 9/1044.0 and 3/555.3, respectively, accounting for an incidence of 1348.0, 862.1 and 540.2 cases per 105 PY. Active TB cases occurring in the first year of TNFi treatment (early TB) per total TB cases were only 3/8, 1/9 and 1/3, respectively, too few to identify statistically significant differences between the 3 LTBI screening protocols. However, less TB cases per total observation time were registered in the QFT group, probably due to the reduced duration of exposure to TNFi. All cases of active TB were registered among patients receiving monoclonal antibodies TNFi agents. We have found no significant risk factors for developing active TB. In our cohort, TB occurring after 1 year of TNFi treatment exceeds 'early TB', suggesting the necessity of further TB prevention measures besides baseline screening for LTBI.

Tenosynovitis US scoring systems follow synovitis and clinical scoring systems in RA and are responsive to change after biologic therapy.

AIMS: To investigate by ultrasonography (US) in a cohort of active RA patients starting biologic therapy the responsiveness of tenosynovitis of wrist and hands compared to the responsiveness of synovitis in a 6 month period follow-up, to compare the responsiveness of finger flexor tenosynovitis with the responsiveness of wrist extensor tenosynovitis and to describe the subclinical synovitis and tenosynovitis in RA patients in clinical remission. MATERIAL AND METHODS: Fifty seven patients with active RA starting biologic therapy were included. Clinical, laboratory, and US evaluations were performed at baseline, 1, and 6 months. US evaluation included wrist and MCPs 2-5 joints, bilaterally for synovitis and extensor tendons compartments 2, 4, and 6 and finger flexors 2-5 for tenosynovitis. Eighteen US scores based on semiquantitative or binary grades were calculated at each visit. Responsiveness of synovitis and tenosynovitis scores was calculated using the standardized response mean (SRM). RESULTS: The responsiveness of US tenosynovitis was lower comparing with the responsiveness of US synovitis but both showed large effect of therapy. Furthermore, tenosynovitis responsiveness was similar to CRP responsiveness (SRM -0.90). Finger flexors tenosynovitis showed a higher responsiveness than extensor tenosynovitis on GS (-0.94 compared to -0.63) and a lower SRM on PD (-0.56 compared to -0.85). Tenosynovitis scores remission was overlapping clinical remission according to CDAI and SDAI in 100% of cases. Overall there was less subclinical tenosynovitis than subclinical synovitis at final visit according to clinical activity indices. CONCLUSION: Tenosynovitis US scoring in RA may be as good as synovitis scoring for characterization of disease activity and responsiveness.

Development of a prognostic score for work disability in Romanian patients with ankylosing spondylitis.

PURPOSE: To develop a prognostic score for predicting work disability (WD) in patients with ankylosing spondylitis (AS) as strong indicator for poor vocational rehabilitation. METHOD: A cross-sectional study was performed in a group of 170 patients with AS, 120 work disabled and 50 still employed. The variables strongly associated with WD were quantified (scored 0-30) - abnormalities of: anterior-posterior radiograph of pelvis, lateral cervical spine radiograph and lung function tests, certain work factors (occupation, physical strain and microclimate), Bath Ankylosing Spondylitis Mobility Index and Bath Ankylosing Spondylitis Functional Index tests. RESULTS: The eight-item score identifies WD with sensitivity of 91.7% and specificity of 85.7%. The scaling properties were fulfilled: internal consistency - Chronbach's alpha 0.73; reliability - intraclass correlation coefficient 0.73; redundancy weak-moderate, with coefficients ranging from 0.032 to 0.797; the discriminative capacity by the significant variations of the score according to the statute (employed or work disabled) and the degree of WD. CONCLUSIONS: The score is a reliable method for assessing the WD risk in patients with AS. It allows a complex evaluation by performing minimal investigations and it is easy to perform. IMPLICATIONS FOR REHABILITATION: Work disability is an important outcome in AS, determined by numerous variables but highly dependent on the national characteristics of economy, social security and healthcare system. The prognostic score for work disability in AS not only contains medical but also socio-demographic and work-related factors and is expected to be a useful tool for specialists to guide the tertiary prevention-oriented rehabilitation measures. Our study suggests the prognostic score to be comprehensive, useful and a reliable method to assess the risk of work disability in AS.

Inter & intra-observer reliability of grading ultrasound videoclips with hand pathology in rheumatoid arthritis by using non- sophisticated internet tools (LUMINA study).

AIM: To evaluate the inter- and intraobserver agreement of a group of European rheumatologist ultrasonographers in grading musculoskeletal ultrasound videoclips posted on the Internet by using a non-sophisticated electronic environment. METHODS: Forty short movie clips (less than 30 secs) were made available over the Internet to all participants. Normal and pathological RA hand joints and tendons were included in the movie clips. In the first phase 30 investigators from European countries were invited to evaluate the clips and to interpret/grade them. No instruction session was held prior to the initiation of the study. For synovitis the requested scoring system included 0 to3 grades and for tenosynovitis a binary variable 0/1; separate evaluations were performed for gray scale (GS) and Power Doppler (PD) examinations. In the second phase the responders were asked to grade the same clips in a different order without having access to their first grading scale. Light's k and Cohen's k were used to analyse inter- and intraobserver reliability. RESULTS: Twenty two European rheumatologists agreed to finalise both study phases. Mean Cohen's κ for intraobserver reliability was 0.614/0.689 for tenosynovitis GS/PD and 0.523/0.621 for synovitis GS/PD. Light's k for interobserver reliability was 0.503 for tenosynovitis evaluation and 0.455 for global (synovitis and tenosynovitis) evaluation. Mean global overall agreement was 84.95% (90.2% for global synovitis). CONCLUSIONS: An over-the-net US evaluation and grading has shown moderate to good reliability. The results could be improved if a training session is added at the beginning of the study.

Trends of rheumatoid arthritis monitorization in Romania.

BACKGROUND: rheumatoid arthritis (RA) is associated with the loss of overall functionality, which leads to substantial economic losses. Second line agents used in RA treatment require careful monitorization in terms of efficiency and tolerability. OBJECTIVE: trends, predictive factors and characteristics of clinical, biological and radiological RA monitorization in a cross sectional observational cohort study, conducted on over 206 patients in Romania, with a 12 months follow up (December 2007 - December 2008). METHOD: Cases were recruited from the south-west region of the country, covering a geographical area of 23 counties. Patients were invited to complete three sets of interviews (collected by post) in a consent letter, containing self reported questionnaires, at 6 months intervals: an original questionnaire (which included quantitative self reported of pain, disease activity and fatigue on visual analogue scale-VAS), Health Assessment Questionnaire-HAQ-Disability and Discomfort Scales and EUROQOL EQ-5D, validated in Romanian (obtaining a user agreement by authors of the original version). RESULTS: analysis was carried out in SPSS 10. The cohort enrolled 206 patients, with the average age of 54.90 +/- 12.67 years, 66% urban, 86.4% women, 29.1% professionally active, 48.5% graduates of primary education. The average disease duration after diagnosis of RA was of 9.40 +/- 8.87 years. The duration of the treatment reported at baseline was of 2.70 +/- 2.64 years. Most patients followed a program of monthly monitoring at a general practitioner (GP) (41.7% at baseline and 37.1% to 12 months). Visits to the rheumatologist followed a monthly regimen (32.3% at baseline and 31.7% to 12 months) or a 2 months interval (19.4% at baseline and 29.6% to 12 months, p = 0.000). Biological monitoring was quarterly (39.6% and 53.2% at 12 months; p = 0.000) or at 2 months interval (26.2% at baseline and 16.7% to 12 months, p = 0.000). X-ray monitoring lacked in over half the cases in a year of disease progression (63.3% at 6 months and 62.2% at 12 months), although it sums between 1 and 3 radiographs to one third of the cases (36.8%), CONCLUSION: generally, in our country, there is a lack of aggregation in the dispensarization algorithm of patients with RA; consequently, the decision is awarded to the human factor. Under these circumstances, some patients are over evaluated. Promoting a dispensarization guide for RA patients could induce benefits both clinically and economically. Therefore, we submit a proposal of recommendations as a guideline for clinical, biological and radiological monitoring, according to the phase and stage of RA.

Rheumatoid arthritis: travelling biological era a Romanian X-ray population.

BACKGROUND: Rheumatoid arthritis (RA) is associated with loss of overall functionality of the locomotion system and it is connected with substantial economic losses. OBJECTIVE: To describe the clinical characteristics and healthcare resource utilization characteristics and to analyze the correlations in a cross-sectional sample of 206 patients in Romania. METHOD: RA cases have been enrolled from southern and western part of the country, covering a surface of 23 counties. RESULTS: Particularly in the literature data, Romanian RA patients become work disabled at 5.65 +/- 5.99 years old after the diagnosis. At cohort level, retirement in the first year after RA diagnosis is of 22.9%. From those, 13% were treated with biologic DMARDs; those on non-biologic DMARDs were 28.6%. In oral therapy group the most prescribed drug is lefunomide (61.2%). RA has an important impact on pain, function and utility, influenced by social factors. Patients' follow up is often based on hospitalization. CONCLUSION: Currently, when the clinician may choose for one certain therapy or another, the social influence is still overwhelming at all the evaluation levels in RA patients, as well as at economic impact.

Correlation between different components of synovial fluid and pathogenesis of rheumatic diseases.

UNLABELLED: Biochemical analysis of synovial fluid is important in orientating the diagnosis of joint effusions. Its composition reflects the metabolic status of synovial tissue correlated with different rheumatic pathologies. The aim of this study was to compare the information provided by usual biochemical tests and proton magnetic resonance spectroscopy (MRS) analysis of synovial fluid, in order to detect potential characteristics of joint effusion correlated to the pathogenesis of arthritis. PATIENTS AND METHODS: This study included 99 synovial fluid samples obtained from patients with different etiology of arthritis--rheumatoid arthritis (RA), osteoarthritis (OA), gout, seronegative spondylarthropathies and septic arthritis, which underwent routine laboratory tests available in the Department of Rheumatology, Cantacuzino Clinical Hospital, Bucharest. Patients were admitted in the hospital between January 2003 and June 2005. Synovial samples were examined in parallel using MRS determination. Spectra have been recorded on a Bruker Avance DRX 400 MHz spectrometer. RESULTS: We obtained a good correlation between biochemical analysis and MRS determination. RA samples have offered the most important information regarding the complex composition of pathological synovial fluid. In addition to the markedly elevated lactate (p < 0.009) and diminished glucose concentration (p < 0.02) in RA samples vs. OA, MRS analysis provides evidence for reduced mean chain length of very-low-density-lipoprotein (VLDL)-associated triacylglycerols (p < 0.05), high levels of ketone bodies (p < 0.05), ceramide (p < 0.02) and citrulline (p < 0.04). OA samples have shown a characteristically increased level of N-glucosamine (p < 0.04) and creatine (p < 0.04). For the other pathologies, there are no characteristic markers detected, except for the extremely increased level of lactate and the decreased concentration of glucose in septic arthritis. CONCLUSIONS: This study gave us the possibility to provide a complex exploration of the biochemical environment of synovial fluid using the MRS method, that offers us the opportunity to understand more about the pathogenesis of rheumatic diseases, to provide information regarding the degree of inflammation, immune infiltration and apoptosis in RA, cartilage degradation and muscular secondary atrophy in OA. The most valuable information is focused on the possibility to have a simultaneous detection of more than 26 different metabolites in synovial fluid samples.

A Romanian instrument to facilitate bone density measurement indication in postmenopausal women.

UNLABELLED: The aim of the study is to find and valid a clinical instrument which identifies the women that need a bone density measurement because of their high risk for osteoporosis. MATERIAL AND METHOD: A number of 356 women were enrolled in this study. They filled in a study formular and their bone density was measured by DEXA exam (dual energy X-ray absorbtiometry) in the lumbar spine and proximal femur. Statistical correlations between the dependent variable minimal T-score and the other variables (clinical risk factors) were established. The most significant osteoporosis risk factor were included in a classification tree for the dependent variable minimal T-score with 5 splits, 5 independent splitting variables and 6 terminal knots. RESULTS: The most significant osteoporosis predictors included in our classification tree are: current weight, decreasing of height, sedentary life, alcohol consumption, number of deliveries. In predicting osteoporosis, the classification tree has high values both for sensitivity and for specificity (88.2%, respectively 74.11%).The osteoporosis prevalence is very high (74.34%) within the group predicted as having osteoporosis (53.7% of all women). The osteoporosis prevalence was 11% within the group predicted as having osteopenia. CONCLUSIONS: The classification tree facilitates a bone density measurement strategy and establishes the criteria for initiation of the treatment in high risk osteoporosis cases. It allows postponing the DEXA-exam for low risk women and selective measurement of the bone density for intermediar osteoporosis risk women.