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ID PMID Title PublicationDate abstract
32166429 Effectiveness of maintenance therapy with methotrexate compared with leflunomide for patie 2020 Sep INTRODUCTION/OBJECTIVES: Evidence regarding the effectiveness of step-down strategies for patients with well-controlled early rheumatoid arthritis (RA) on a combination of methotrexate (MTX) and leflunomide (LEF) is currently lacking. METHOD: The Care in early RA (CareRA) trial is a 2-year randomized pragmatic trial comparing different remission induction strategies in treatment-naïve patients with early RA. For this study, we included participants who achieved low disease activity (LDA) (DAS28-CRP ≤ 3.2) between 40 to 52 weeks after starting a combination of MTX, LEF, and a prednisone bridging scheme followed by a treat-to-target approach. Patients were re-randomized to a maintenance monotherapy of either MTX 15 mg weekly or LEF 20 mg daily. Remission rates (DAS28-CRP < 2.6) at week 65 counted from re-randomization, as well as drug retention rates and safety during the 65 weeks of follow-up, were compared. RESULTS: Remission rates at week 65 after re-randomization were numerically higher in patients assigned to MTX (29/32; 90.6%) compared with patients on LEF (20/27; 74.1%) (p = 0.091). Of patients assigned to MTX, 60% (19/32) maintained LDA while continuing their assigned monotherapy until week 65 after re-randomization versus 44% (12/27) in the LEF group (p = 0.25). Patients re-randomized to MTX were more frequently in LDA measured by Clinical Disease Activity Index (32/32; 100%) compared with patients on LEF (23/27; 85.2%) (p = 0.024) 65 weeks after re-randomization. According to survival analyses, the probability of maintaining MTX monotherapy was higher (81%) than maintaining LEF monotherapy (55%) for 65 weeks (p = 0.025) after re-randomization. Safety analysis after re-randomization showed a good safety profile in both groups. CONCLUSION: MTX monotherapy seems not significantly more efficacious as maintenance treatment compared with LEF monotherapy but has a better retention rate and is well tolerated in early RA patients in LDA after combination therapy with both. TRIAL REGISTRATION: Clinical trials NCT01172639 Key points • Methotrexate should be preferred over leflunomide as maintenance therapy after an initial intensive combination of these two drugs. • Methotrexate shows a better retention rate to leflunomide as maintenance therapy in this context.
32887683 Genomic risk scores for juvenile idiopathic arthritis and its subtypes. 2020 Dec OBJECTIVES: Juvenile idiopathic arthritis (JIA) is an autoimmune disease and a common cause of chronic disability in children. Diagnosis of JIA is based purely on clinical symptoms, which can be variable, leading to diagnosis and treatment delays. Despite JIA having substantial heritability, the construction of genomic risk scores (GRSs) to aid or expedite diagnosis has not been assessed. Here, we generate GRSs for JIA and its subtypes and evaluate their performance. METHODS: We examined three case/control cohorts (UK, US-based and Australia) with genome-wide single nucleotide polymorphism (SNP) genotypes. We trained GRSs for JIA and its subtypes using lasso-penalised linear models in cross-validation on the UK cohort, and externally tested it in the other cohorts. RESULTS: The JIA GRS alone achieved cross-validated area under the receiver operating characteristic curve (AUC)=0.670 in the UK cohort and externally-validated AUCs of 0.657 and 0.671 in the US-based and Australian cohorts, respectively. In logistic regression of case/control status, the corresponding odds ratios (ORs) per standard deviation (SD) of GRS were 1.831 (1.685 to 1.991) and 2.008 (1.731 to 2.345), and were unattenuated by adjustment for sex or the top 10 genetic principal components. Extending our analysis to JIA subtypes revealed that the enthesitis-related JIA had both the longest time-to-referral and the subtype GRS with the strongest predictive capacity overall across data sets: AUCs 0.82 in UK; 0.84 in Australian; and 0.70 in US-based. The particularly common oligoarthritis JIA also had a GRS that outperformed those for JIA overall, with AUCs of 0.72, 0.74 and 0.77, respectively. CONCLUSIONS: A GRS for JIA has potential to augment clinical JIA diagnosis protocols, prioritising higher-risk individuals for follow-up and treatment. Consistent with JIA heterogeneity, subtype-specific GRSs showed particularly high performance for enthesitis-related and oligoarthritis JIA.
33092242 Biological and Clinical Changes in a Pediatric Series Treated with Off-Label JAK Inhibitor 2020 Oct 20 Off-label use of medications is still a common practice in pediatric rheumatology. JAK inhibitors are authorized in adults in the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Although their use is not authorized yet in children, JAK inhibitors, based on their mechanism of action and on clinical experiences in small series, have been suggested to be useful in the treatment of pediatric interferon-mediated inflammation. Accordingly, an increased interferon score may help to identify those patients who might benefit of JAK inhibitors. We describe the clinical experience with JAK inhibitors in seven children affected with severe inflammatory conditions and we discuss the correlation between clinical features and transcriptomic data. Clinical improvements were recorded in all cases. A reduction of interferon signaling was recorded in three out of seven subjects at last follow-up, irrespectively from clinical improvements. Other signal pathways with significant differences between patients and controls included upregulation of DNA repair pathway and downregulation of extracellular collagen homeostasis. Two patients developed drug-related adverse events, which were considered serious in one case. In conclusion, JAK inhibitors may offer a valuable option for children with severe interferon-mediated inflammatory disorders reducing the interferon score as well as influencing other signal pathways that deserve future studies.
32218427 Rheumatologic manifestations of hepatitis C in the era of direct-acting antiviral agents. 2020 Sep Beyond the classic hepatic complications, hepatitis C (HCV) infection is considered as a systemic disease, since extrahepatic manifestations become clinically evident in 40% to 70% of the patients and it can frequently include rheumatic ones. Furthermore, HCV can promote the production of several autoantibodies, thus complicating the differential diagnosis between primitive and HCV-related rheumatic disorders. The recent development of direct-acting antivirals (DAA) against HCV has revolutionized the field, reducing the damage stemming from systemic inflammatory phenomena and persistent immune activation associated with continuous HCV replication. Our review focuses on the main rheumatologic manifestations associated with chronic HCV infection as well as the impact of DAA interferon-free treatments on such extrahepatic clinical involvement.
32003472 Recurrent breast amyloidosis associated with Sjögren's syndrome: A case report with descr 2020 Mar We describe the case of a 41-year-old woman with primary Sjögren's syndrome (SS) who presented multiple recurrences of breast amyloidosis. Each recurrence of breast amyloidosis showed different sonographic features, potentially mimicking malignancy. We briefly discuss the possible cause of this variability in imaging features based on the radiologic-histologic correlation.
31692065 Clinical significance of serum bilirubin in primary Sjögren syndrome patients. 2020 Mar OBJECTIVE: The purpose of our research was to demonstrate the clinical significance of serum bilirubin in primary Sjögren syndrome patients (pSS). PATIENTS AND METHODS: A total of 116 patients with primary Sjögren syndrome and 138 matched individuals were included in our study. The laboratory parameters of patients with pSS and healthy controls were retrospectively analyzed. RESULTS: Serum total bilirubin, direct bilirubin, and indirect bilirubin were significantly reduced (P < .001, P = .001, P < .001) while ESR was significantly increased (P < .001) in patients with pSS when compared with healthy checkup individuals. Statistically, the AUC in patients with pSS is as follows: TBIL = 0.77, P < .001, cutoff value = 7.96; DBIL = 0.617, P = .001 cutoff value = 2.2; and IBIL = 0.786, P < .001 cutoff value = 4.5. Furthermore, our study revealed that TBIL, DBIL, and IBIL were significantly negativity related to ESR (r = -.406, P < .001; r = -.206, P = .026; r = -.429, P < .001). Interestingly, multiple linear regression analysis showed that when adjusted for sex, age, ALT, and AST, the levels of TBIL, DBIL, and IBIL in patients with pSS were independently correlated with ESR. CONCLUSIONS: This study found that the levels of serum bilirubin were reduced and the inflammatory marker was elevated in patients with pSS. Additionally, serum bilirubin was negatively related with ESR and TBIL, DBIL, and IBIL can be used in the clinical diagnosis and follow-up visits of the patients with pSS.
33035290 Lactoferrin Concentration in Human Tears and Ocular Diseases: A Meta-Analysis. 2020 Oct 1 PURPOSE: To evaluate the potential of lactoferrin (Lf) as a diagnostic biomarker for ocular diseases using a meta-analytic approach. METHODS: All original studies reporting an estimate of the average Lf concentration in healthy subjects and those affected by ocular diseases were searched up to March 2020. The DerSimonian and Laird method was used to calculate the random effects pooled mean difference and the corresponding 95% confidence interval (CI) in Lf concentration between healthy subjects and those affected by dry eye (DE), Sjögren syndrome (SS), and diabetic retinopathy, separately. The presence of between-study heterogeneity was evaluated using the Cochran's Q test and the I2 index. Stratified analyses were performed to assess potential sources of heterogeneity and influence and cumulative analyses to evaluate the robustness of the results obtained. Publication bias was also evaluated using funnel plot and the Egger's test. RESULTS: The pooled mean differences in Lf concentrations between healthy subjects and those with DE, Sjögren syndrome, and diabetic retinopathy were respectively 0.62 (95% CI, 0.35-0.89) for DE, 3.78 (95% CI, -6.64 to 14.17), and 0.19 (95% CI, -4.00 to 4.39). Regarding DE, the stratified analysis showed that geographical area (P value Q test < 0.0001) and sample size (P < 0.0005) were sources of heterogeneity. Moreover, no study substantially influenced the results obtained and the pooled mean difference became statistically significant after a sample size of 220. Publication bias may affect the results of DE. CONCLUSIONS: The results of the current meta-analysis suggest that Lf level in tears is a good candidate as dry eye syndrome diagnostic biomarker.
32385802 Neurologic, clinical, and immunologic features in a cohort of HTLV-1 carriers with high pr 2020 Aug A high proviral load (PVL) is recognized as a risk factor for human T cell leukemia virus-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but there is a lack of prospective studies evaluating whether or not HTLV-1 carriers with high PVL are at risk of developing HAM/TSP or other HTLV-1-related diseases. Here, we compare the incidence of clinical manifestations and the cytokine levels in 30 HTLV-1 carriers with high (> 50,000 copies/10(6) PBMC) and an equal number of subjects with low proviral load. Participants were followed for 3 to 16 years (median of 11 years). The PVL, IFN-γ, TNF, and IL-10 levels were quantified at entry and at the end of the follow-up. Among the self-reported symptoms in the initial evaluation, only the presence of paresthesia on the hands was more frequent in the group with high PVL (p < 0.04). The production of IFN-γ was higher in the group with high PVL group (median of 1308 versus 686 pg/ml, p < 0.011) when compared with the control group in the first assessment. There was no difference in the occurrence of urinary symptoms or erectile dysfunction, periodontal disease, Sicca syndrome, and neurologic signs between the two groups during the follow-up. The observation that none of the HTLV-1 carriers with high PVL and with exaggerated inflammatory response progressed to HAM/TSP indicates that other factors in addition to the PVL and an exaggerated immune response are involved in the pathogenesis of HAM/TSP.
30273264 Atypical Chronic Inflammatory ANCA-Positive Deforming Arthritis After Cocaine-Levamisole E 2020 Jan BACKGROUND/OBJECTIVE: Immunostimulatory drugs including immune checkpoint inhibitors and levamisole can induce inflammatory disease including vasculitis, rashes, tissue necrosis, and arthritis. METHODS: This prospective cohort study determined the 5-year outcomes of cocaine-levamisole-induced inflammatory disease as to outcomes and survival. Thirty-one consecutive cocaine-levamisole autoimmune patients and 45 primary vasculitis patients were characterized as to clinical differentiating features, antineutrophil cytoplasmic antibody (ANCA) status, treatment, the presence of acute and chronic arthritis, and 5-year outcome. RESULTS: Seventy-one percent (22/31) of cocaine-levamisole vasculopathy cases were ANCA positive (86% p-ANCA and 14% c-ANCA), whereas 53% (23/45) of the primary vasculitis were ANCA positive (p = 0.04). The ANCA-positive cocaine-levamisole cohort at onset were characterized by younger age (45 ± 12 vs 53 ± 14 years, p = 0.04), superficial skin necrosis (82% vs 54%, p = 0.036), depressed complement C3 (27% vs 4%, p = 0.33), antiphospholipid antibodies (50% vs 4%, p < 0.001), neutropenia (18% vs 0%, p = 0.044), and elevated antimyeloperoxidase (MPO) antibody levels (100% vs 67%, p < 0.001). Chronic cocaine-levamisole disease was characterized by severe cicatrical deformities of the face and extremities (45.5% vs 8.3%, p = 0.005). Arthralgias (71% vs 82%, p = 0.19) and acute arthritis (33% vs 32%, p = 0.25) were similar between the 2 groups. However, a substantial proportion cocaine-levamisole-induced autoimmune patients (18% vs 0%, p = 0.045) developed a chronic deforming inflammatory arthritis that was rheumatoid factor, anti-cyclic-citrillinated antibody antibody, and HLA-B27 negative, but p-ANCA-and MPO antibody positive. CONCLUSIONS: Patients exposed to cocaine-levamisole may develop serious chronic sequelae including cicatrical cutaneous and facial deformities and an atypical seronegative, p-ANCA and MPO antibody-positive, HLA-B27-negative chronic deforming inflammatory arthritis.
32618923 Periprosthetic Joint Infection in Patients Who Have Multiple Prostheses in Place: What Sho 2020 Jul 1 BACKGROUND: Although periprosthetic joint infection (PJI) can affect multiple joints concurrently, the majority of patients with multiple prosthetic joints present with PJI of a single joint. Data regarding the optimal management of these patients are limited. We aimed to identify the prevalence, risk factors for a subsequent PJI, and clinical circumstances of PJI in patients with multiple prosthetic joints. METHODS: We retrospectively reviewed the clinical records of 197 patients with ≥2 total joint prostheses in place who presented with PJI from 2000 to 2017. The average follow-up was 3.6 years (range, 0.5 to 17 years). Demographic data and risk factors for synchronous or metachronous PJI were identified. The time from the initial to the second PJI and organism profile data were collected as well. The workup for other joints with a prosthesis in place at the time of the initial PJI was noted. RESULTS: Among the 197 patients with PJI and multiple joint prostheses in situ, 37 (19%) developed PJI in another joint; 11 had a synchronous PJI and 26 had a metachronous PJI. The average time between the first and the second infection in the metachronous cases was 848 days (range, 20 to 3,656 days). Females and patients with an initial PJI with methicillin-resistant Staphylococcus aureus (MRSA) were more likely to have a metachronous PJI, and patients with rheumatoid arthritis had an increased risk of a second (metachronous or synchronous) PJI. Three of 11 patients in the synchronous group and 19% (5) of the 26 in the metachronous group had bacteremia at the time of the initial PJI compared with 12% (19) of the 160 with a single PJI. The percentage of negative cultures increased from 10% for the initial PJIs to 38% for the metachronous PJIs. CONCLUSIONS: Patients who have multiple prosthetic joints in place and present with PJI of a single joint are at risk of developing PJI in another joint. Female sex, rheumatoid arthritis, bacteremia at presentation, and infection with MRSA appear to be risk factors for PJI of another joint. Clinical evaluation of the other prosthetic joint(s) should be carried out in all patients and aspiration of those joint(s) should be considered for patients with any of the above risk factors. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
32021123 Treatment Mode Preferences in Rheumatoid Arthritis: Moving Toward Shared Decision-Making. 2020 PURPOSE: Current knowledge of the reasons for patients' preference for rheumatoid arthritis (RA) treatment modes is limited. This study was designed to identify preferences for four treatment modes, and to obtain in-depth information on the reasons for these preferences. PATIENTS AND METHODS: In this multi-national, cross-sectional, qualitative study, in-depth interviews were conducted with adult patients with RA in the United States, France, Germany, Italy, Spain, Switzerland, the United Kingdom, and Brazil. Patients' strength of preference was evaluated using a 100-point allocation task (0-100; 100=strongest) across four treatment modes: oral, self-injection, clinic-injection, and infusion. Qualitative descriptive analysis methods were used to identify, characterize, and summarize patterns found in the interview data relating to reasons for these preferences. RESULTS: 100 patients were interviewed (female, 75.0%; mean age, 53.9 years; mean 11.6 years since diagnosis). Among the four treatment modes, oral administration was allocated the highest mean (standard deviation) preference points (47.3 [33.1]) and was ranked first choice by the greatest percentage of patients (57.0%), followed by self-injection (29.7 [27.7]; 29.0%), infusion (15.4 [24.6]; 16.0%), and clinic-injection (7.5 [14.1]; 2.0%). Overall, 56.0% of patients had a "strong" first-choice preference (ie, point allocation ≥70); most of these patients chose oral (62.5%) vs self-injection (23.2%), infusion (10.7%), or clinic-injection (3.6%). Speed and/or ease of administration were the most commonly reported reasons for patients choosing oral (52.6%) or self-injection (55.2%). The most common reasons for patients not choosing oral or self-injection were not wanting to take another pill (37.2%) and avoiding pain due to needles (46.5%), respectively. CONCLUSION: These data report factors important to patients regarding preferences for RA treatment modes. Patients may benefit from discussions with their healthcare professionals and/or patient support groups, regarding RA treatment modes, to facilitate shared decision-making.
33282536 Complications and Factors Associated with Reoperation following Total Wrist Fusion. 2020 Dec Background  Total wrist fusion can be elected to relieve pain in patients with osteoarthritis and rheumatoid arthritis. This study aimed to investigate the overall complications and the factors associated with reoperation and soft tissue complication after total wrist fusion. Methods  We retrospectively identified adult patients who underwent total wrist fusion using Current Procedural Terminology (CPT) codes, International Classification of Diseases, Ninth and Tenth Revision (ICD-9 and ICD-10) and verified these by medical chart review. We included patients ( n  = 215) who were treated at a single institutional system from January 1, 2002 to January 1, 2019. The mean age was 53.3 ± 15.0 years and the median follow-up was 6.1 years (interquartile range [IQR] =1.7-9.0). The most common indications for wrist fusion included inflammatory arthritis ( n  = 66, 31%), degenerative arthritis ( n  = 59, 27%), and posttraumatic arthritis ( n  = 47, 22%). All wrist fusions were performed using a dorsal fusion plate or dorsal spanning plate, either with a local autograft ( n  = 167, 78%), iliac crest autograft ( n  = 2, 1.0%), allograft ( n  = 7, 3.3%), a combination of both ( n  = 16, 7.4%), or without a graft ( n  = 23, 11%). We performed a multivariable logistic regression to evaluate factors associated with reoperation. In addition, we performed a similar analysis to identify the factors associated with soft tissue complication after total wrist fusion. Results  Forty-one (19%) patients underwent reoperation at a median of 6.9 months (IQR = 3.9-18). The indications included symptomatic implants ( n  = 12, 27%), implant failures ( n  = 8, 20%), infections ( n  = 7, 17%), and nonunions ( n  = 6, 15%). In multivariable analysis, total wrist fusion of the dominant hand (odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.1-4.7, p  = 0.033) was associated with a higher reoperation rate. Soft tissue complications occurred in 20 patients (9.3%) consisting of hematomas ( n  = 8, 3.7%), observed blistering ( n  = 5, 2.3%), and observed wound dehiscence ( n  = 4, 1.9%). In multivariable analysis, smoking (OR: 2.5, CI: 0.95-6.4, p  = 0.010) was independently associated with soft tissue complication after total wrist fusion. Seventy-two (33%) patients had a postoperative complication including symptomatic hardware ( n  = 16, 7.4%), implant failure ( n  = 11, 5.1%), infection ( n  = 11, 5.1%), nonunion ( n  = 8, 3.7%), and carpal tunnel syndrome ( n  = 4, 1.9%). Conclusion  Roughly one-third (33%) of the patients undergoing total wrist fusion experience a postoperative complication and 19% of the patients underwent a reoperation. Total wrist fusion of the dominant hand results in higher reoperation rates. The risk of a soft tissue complication after total wrist fusion is increased in smokers.
33083414 Rapid remission of refractory synovitis, acne, pustulosis, hyperostosis, and osteitis synd 2020 Oct 6 BACKGROUND: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoinflammatory disease for which clinical treatment has not been standardized. Janus kinase (JAK) inhibitors represent a novel therapeutic option for rheumatoid arthritis, psoriatic arthritis, and some other autoinflammatory diseases. However, the clinical utility of JAK inhibitors in treating SAPHO syndrome has not been thoroughly investigated. In this study, we describe a patient with SAPHO syndrome who failed to respond to conventional treatment but demonstrated a remarkable and rapid response to the JAK inhibitor tofacitinib. CASE SUMMARY: A 62-year-old female patient presented with swelling and pain at the sternoclavicular joints, back pain that limited her activities, arthralgia in the right knee, and cutaneous lesions. Her symptoms were unresponsive to nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, Tripterygium wilfordii hook f, and bisphosphonates. SAPHO syndrome was diagnosed in accordance with dermatological and osteoarticular manifestations and abnormal inflammatory factors. Multiple image studies have illustrated bone lesions and pathological fractures of vertebral bodies. Oral treatment with tofacitinib at 5 mg twice daily with methotrexate and bisphosphonates was initiated. The patient reported that her pain symptoms were relieved after 3 d and her cutaneous lesions were reduced after 4 wk of treatment. Vertebral lesions were improved after 6 mo on tofacitinib. No serious adverse effects were noted. CONCLUSION: JAK inhibitor therapy may be a promising strategy to treat SAPHO syndrome.
32708322 Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immun 2020 Jul 21 Some coronavirus disease 2019 (COVID-19) patients develop acute pneumonia which can result in a cytokine storm syndrome in response to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. The most effective anti-inflammatory drugs employed so far in severe COVID-19 belong to the cytokine-directed biological agents, widely used in the management of many autoimmune diseases. In this paper we analyze the efficacy of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea leaves and a well-known antioxidant, in counteracting autoimmune diseases, which are dominated by a massive cytokines production. Indeed, many studies registered that EGCG inhibits signal transducer and activator of transcription (STAT)1/3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factors, whose activities are crucial in a multiplicity of downstream pro-inflammatory signaling pathways. Importantly, the safety of EGCG/green tea extract supplementation is well documented in many clinical trials, as discussed in this review. Since EGCG can restore the natural immunological homeostasis in many different autoimmune diseases, we propose here a supplementation therapy with EGCG in COVID-19 patients. Besides some antiviral and anti-sepsis actions, the major EGCG benefits lie in its anti-fibrotic effect and in the ability to simultaneously downregulate expression and signaling of many inflammatory mediators. In conclusion, EGCG can be considered a potential safe natural supplement to counteract hyper-inflammation growing in COVID-19.
32709717 Egr2 and 3 control inflammation, but maintain homeostasis, of PD-1(high) memory phenotype 2020 Sep The transcription factors Egr2 and 3 are essential for controlling inflammatory autoimmune responses of memory phenotype (MP) CD4 T cells. However, the mechanism is still unclear. We have now found that the Egr2(+) subset (PD-1(high) MP) of MP CD4 T cells expresses high levels of checkpoint molecules (PD-1 and Lag3) and also markers of effector T cells (CXCR3 and ICAM-1). Egr2/3 are not required for PD-1(high) MP CD4 cell development but mediate a unique transcriptional programme that effectively controls their inflammatory responses, while promoting homeostatic proliferation and adaptive responses. Egr2 negative PD-1(high) MP CD4 T cells are impaired in homeostatic proliferation and adaptive responses against viral infection but display inflammatory responses to innate stimulation such as IL-12. PD-1(high) MP CD4 T cells have recently been implicated in rheumatoid arthritis pathogenesis, and we have now found that Egr2 expression is reduced in PD-1(high) MP CD4 T cells from patients with active rheumatoid arthritis compared with healthy controls. These findings demonstrate that Egr2/3 control the inflammatory responses of PD-1(high) MP CD4 T cells and maintain their adaptive immune fitness.
33145983 Total Knee Arthroplasty in Patients with Unsuspected Tuberculosis of the Joint: A Report o 2020 Dec OBJECTIVES: To provide a case series and systematic review that explores the clinical manifestations, treatments, and methods for defining tuberculosis diagnoses in patients who have undergone total knee arthroplasty (TKA). METHODS: Four patients (three women, one man; average age, 59.5 ± 8.89 years; range, 48-69 years) underwent TKA and were subsequently treated for previously unsuspected knee tuberculosis between January 2013 and December 2019. We also reviewed published cases of tuberculous periprosthetic joint infections (TBPJIs) following TKA through databases of MEDLINE/PubMed, the Cochrane Library, and EMBASE. We reviewed studies that were published between January 1980 and December 2019. RESULTS: In our four cases, the preoperative diagnoses were osteoarthritis (n = 2), rheumatoid arthritis (one case), and Charcot's arthropathy (one case). The main clinical manifestations were knee swelling and pain, without fever, weakness, or weight loss. Comorbidities included multiple joints with rheumatoid arthritis or Charcot's arthropathy, diabetes mellitus, and uremia. One patient had a history of lumbar tuberculosis treated with debridement and intervertebral fusion. Preoperative elevated erythrocyte sedimentation rates (ESRs) were detected in all cases, and elevated C-reactive protein (CRP) levels were observed in three cases. The tuberculosis diagnoses were confirmed via histopathologic analysis (three cases) and second-generation sequencing (one case). Three patients received antituberculosis therapy for 1 year, without surgical intervention. Two-stage exchange arthroplasty was performed in one patient because of prosthesis loosening. Within an average follow-up period of 24.75 months, tuberculosis reactivation was not observed and overall functional improvement was demonstrated. Forty-four TBPJI cases were reported in the literature between January 1980 and December 2019. Most (59.09%) occurred within the first year after the index arthroplasty, and the diagnoses were confirmed by culturing Mycobacterium tuberculosis in 88.64% of cases. Favorable outcomes were achieved in 90.91% of the patients who did not undergo surgery, 71.43% of those treated with debridement, 93.33% undergoing revision arthroplasty, and in 90.91% of those undergoing resection and arthrodesis. CONCLUSIONS: Clinical manifestations of knee tuberculosis and TBPJI are atypical. Thus, attention should be paid to finding the causes of increased ESRs and CRP levels, particularly in patients with weakened immune functioning, before performing TKA. Pathological examination is an effective method for diagnosing tuberculosis, although sending multiple specimens for pathological examination is necessary.
32910753 Disease-modifying antirheumatic drug prescription patterns in adult rheumatoid arthritis p 2020 Sep 3 OBJECTIVE: To describe disease-modifying antirheumatic drug (DMARD) patterns in routine clinical practice in adult rheumatoid arthritis (RA) patients and to ascertain the reasons for methotrexate (MTX) discontinuation. METHODS: A cross-sectional observational study was conducted from March to October 2014 at the Rheumatology Units of seven hospitals in Spain. In a single visit, the treating rheumatologist completed an online case report form. This report contained sociodemographic and RA variables. This study was conducted in accordance with Good Clinical Practice and local and national research legislations. RESULTS: A total of 301 patients (71% women) with a mean age of 56.7±14.0 years and disease duration of 3.6±1.5 years were examined. The patients had RA with moderate disease activity, at least one poor prognostic factor, and comorbidities. The mean time between RA diagnosis and prescription of the first conventional synthetic DMARD (csDMARD) was 2.4±6.0 months. A total of 295 patients (98%) started the first csDMARD on monotherapy. MTX was the most-prescribed first-line drug (n=233, 79%). The mean treatment time of the first-line csDMARD was 27.0±19.4 months. Of these patients, 98% progressed to a second-line csDMARD; 118 patients were changed to another DMARD, mainly due to inefficacy (51, 37%), adverse events (AEs, 37, 27%), or intolerance (18, 13%). The use of MTX as second-line therapy reduced from 79% to 51%. At the time of the study, 200 patients (66%) received a csDMARD as monotherapy and 45 (15%) a combination of ≥2 csDMARDs. Fifty-five (18%) patients were being treated with a biological drug in monotherapy (16, 29%) or in a combination with a csDMARD (39, 71%), mainly MTX, 147 patients (57%) received steroids. Biological DMARD were prescribed as the second line for 42% of patients and 51% of patients received the third-line therapy or beyond. The rate of AEs that motivated a change in the csDMARD was 34%. CONCLUSION: MTX was the most-used csDMARD as first and second-line therapy together with corticosteroids. The combination of two or more csDMARDs as first-line treatment was very infrequent. MTX toxicity and intolerance were higher and more significant than inefficacy but progressively decreased with use.
32797280 Reproductive health counseling and contraceptive use in Mexican women with rheumatic disea 2021 Feb BACKGROUND: There is an overall increased risk of adverse pregnancy outcomes and maternal morbidity in patients with most autoimmune rheumatic diseases (ARD); outcomes are generally improved when the pregnancy is planned and the disease is in control. OBJECTIVE: The objective of the present study was to describe the sexual and reproductive health characteristics and contraceptive use of Mexican women in childbearing age with ARD. METHODS: We conducted an observational, cross-sectional, and descriptive study. All non-pregnant childbearing age women with an ARD were invited to participate. A self-administered questionnaire of ten items that included questions about sexuality, use of contraceptive methods, pregnancy desire, and contraceptional counseling was applied. RESULTS: A total of 135 women were evaluated. The median age was 33 (25-39) years. Contraceptive use was referred by 49 (71%) of the patients that had sexual activity the last month, while 20 (28.9%) patients denied use. From the patients who had initiated sexual activity (N = 112), 41 (36.6%) did not use any contraceptive method, and 16 (14%) used a method classified as ineffective. The question about contraceptive counseling was answered by 112 patients. Eighty (70.4%) said they had received counseling from health-professional and 64 (57.1%) from their rheumatologist. A total of 57% of the women with teratogenic drugs did not employ a contraception method. CONCLUSION: Contraceptive use and reproductive health counseling are suboptimal in Mexican women with ARD. A high proportion of women taking teratogenic drugs did not employ a highly effective contraceptive method. Strategies to improve reproductive and sexual health are necessary.
33329046 Inflammation and Skeletal Muscle Wasting During Cachexia. 2020 Cachexia is the involuntary loss of muscle and adipose tissue that strongly affects mortality and treatment efficacy in patients with cancer or chronic inflammatory disease. Currently, no specific treatments or interventions are available for patients developing this disorder. Given the well-documented involvement of pro-inflammatory cytokines in muscle and fat metabolism in physiological responses and in the pathophysiology of chronic inflammatory disease and cancer, considerable interest has revolved around their role in mediating cachexia. This has been supported by association studies that report increased levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in some, but not all, cancers and in chronic inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and rheumatoid arthritis (RA). In addition, preclinical studies including animal disease models have provided a substantial body of evidence implicating a causal contribution of systemic inflammation to cachexia. The presence of inflammatory cytokines can affect skeletal muscle through several direct mechanisms, relying on activation of the corresponding receptor expressed by muscle, and resulting in inhibition of muscle protein synthesis (MPS), elevation of catabolic activity through the ubiquitin-proteasomal system (UPS) and autophagy, and impairment of myogenesis. Additionally, systemic inflammatory mediators indirectly contribute to muscle wasting through dysregulation of tissue and organ systems, including GCs via the hypothalamus-pituitary-adrenal (HPA) axis, the digestive system leading to anorexia-cachexia, and alterations in liver and adipocyte behavior, which subsequently impact on muscle. Finally, myokines secreted by skeletal muscle itself in response to inflammation have been implicated as autocrine and endocrine mediators of cachexia, as well as potential modulators of this debilitating condition. While inflammation has been shown to play a pivotal role in cachexia development, further understanding how these cytokines contribute to disease progression is required to reveal biomarkers or diagnostic tools to help identify at risk patients, or enable the design of targeted therapies to prevent or delay the progression of cachexia.
32373790 Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohis 2020 Jun The term cytokine storm syndromes describes conditions characterised by a life-threatening, fulminant hypercytokinaemia with high mortality. Cytokine storm syndromes can be genetic or a secondary complication of autoimmune or autoinflammatory disorders, infections, and haematological malignancies. These syndromes represent a key area of interface between rheumatology and general medicine. Rheumatologists often lead in management, in view of their experience using intensive immunosuppressive regimens and managing cytokine storm syndromes in the context of rheumatic disorders or infection (known as secondary haemophagocytic lymphohistiocytosis or macrophage activation syndrome [sHLH/MAS]). Interleukin (IL)-1 is pivotal in hyperinflammation. Anakinra, a recombinant humanised IL-1 receptor antagonist, is licenced at a dose of 100 mg once daily by subcutaneous injection for rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still's disease, and cryopyrin-associated periodic syndromes. In cytokine storm syndromes, the subcutaneous route is often problematic, as absorption can be unreliable in patients with critical illness, and multiple injections are needed to achieve the high doses required. As a result, intravenous anakinra is used in clinical practice for sHLH/MAS, despite this being an off-licence indication and route of administration. Among 46 patients admitted to our three international, tertiary centres for sHLH/MAS and treated with anakinra over 12 months, the intravenous route of delivery was used in 18 (39%) patients. In this Viewpoint, we describe current challenges in the management of cytokine storm syndromes and review the pharmacokinetic and safety profile of intravenous anakinra. There is accumulating evidence to support the rationale for, and safety of, intravenous anakinra as a first-line treatment in patients with sHLH/MAS. Intravenous anakinra has important clinical relevance when high doses of drug are required or if patients have subcutaneous oedema, severe thrombocytopenia, or neurological involvement. Cross-speciality management and collaboration, with the generation of international, multi-centre registries and biobanks, are needed to better understand the aetiopathogenesis and improve the poor prognosis of cytokine storm syndromes.