Morbimortality in adult patients with septic arthritis: a three-year hospital-based study.

BACKGROUND: The objective of this ambispective study was to determine outcomes and associated factors for adult patients with confirmed septic arthritis (SA). METHODS: All adult patients admitted to Amiens University Hospital between November 2010 and December 2013 with confirmed SA were included in the study. Patients with prosthetic joint infections were excluded. A statistical analysis was performed in order to identify risk factors associated with a poor outcome (including mortality directly attributable to SA). RESULTS: A total of 109 patients (mean ± SD age: 60.1 ± 20.1; 74 male/35 females) were diagnosed with SA during the study period. The most commonly involved sites were the small joints (n = 34, 31.2 %) and the knee (n = 25, 22.9 %). The most frequent concomitant conditions were cardiovascular disease (n = 45, 41.3 %) and rheumatic disease (n = 39, 35.8 %). One hundred patients (91.7 %) had a positive microbiological culture test, with Staphylococcus aureus as the most commonly detected pathogen (n = 59, 54.1 %). Mortality directly attributable to SA was relatively infrequent (n = 6, 5.6 %) and occurred soon after the onset of SA (median [range]: 24 days [1-42]). Major risk factors associated with death directly attributable to SA were older age (p = 0.023), high C-reactive protein levels (p = 0.002), diabetes mellitus (p = 0.028), rheumatoid arthritis and other inflammatory rheumatic diseases (p = 0.021), confusion on admission (p = 0.012), bacteraemia (p = 0.015), a low creatinine clearance rate (p = 0.009) and the presence of leg ulcers/eschars (p = 0.003). The median duration of follow-up (in patients who survived for more than 6 months) was 17 months [6-43]. The proportion of poor functional outcomes was high (31.8 %). Major risk factors associated with a poor functional outcome were older age (0.049), hip joint involvement (p = 0.003), the presence of leg ulcers/eschars (p = 0.012), longer time to presentation (0.034) and a low creatinine clearance rate (p = 0.013). CONCLUSIONS: In a university hospital setting, SA is still associated with high morbidity and mortality rates.

Decrease of Tocilizumab Dose in Patients with Rheumatoid Arthritis: A Pilot Study.

BACKGROUND: The efficacy and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) are well demonstrated. Doses of 4 and 8 mg/kg are used intravenously. The objective of our study was to report the efficacy and safety for a set of patients who had an 8 mg/kg doze of TCZ and for another set who had this treatment first at a dose of 8 followed by 4 mg/kg. METHODS: All RA patients treated with TCZ in a University Hospital Centre Department of Rheumatology between January 2010 and December 2014 were included. Sixty-three patients received TCZ at a dose of 8 mg/kg and 19 patients received this treatment first receiving a dose of 8 mg/kg decreased to 4 mg/kg. The demographic characteristics, the clinical response and adverse events were reported. RESULTS: At the end of follow-up, 48% of patients were in clinical remission defined by disease activity score based on 28 joints with an erythrocyte sedimentation rate <2.6 in the 8 mg/kg group and 74% of patients in the 8-4 mg/kg. The rates of severe infections were 4.8 per 100 patients-years (PY) in the 8 mg/kg group and 2.9 per 100 PY in the 8 then 4 mg/kg. The infections were mainly pulmonary, ENT and skin infections. CONCLUSION: Our study reported the efficacy and safety of the TCZ in patients with RA in 'real life' with the dose of 8 mg/kg or 8 then 4 mg/kg.

Lymphoma complicating rheumatoid arthritis: results from a French case-control study.

OBJECTIVES: To study the characteristics of B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence. METHODS: A multicentre case-control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma. RESULTS: 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma. CONCLUSION: Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA.

Therapeutic Maintenance of Baricitinib and Tofacitinib in Real Life.

BACKGROUND: Janus kinase inhibitors (JAKis) represent a new alternative to treat rheumatoid arthritis (RA). The objective of this study was to evaluate the effectiveness, tolerance profile, and maintenance of these treatments (tofacitinib and baricitinib) in real life. METHODS: All patients in the rheumatology department of Amiens University Hospital treated by JAKis for RA were included from 1 October 2017 to 20 May 2020. Clinical and biological data were provided retrospectively in this observational and single-center study. We aimed to study the JAKi maintenance rate at 12 months and their clinical and biological safety profiles. RESULTS: Fifty-five patients were included. Drug maintenance at 12 months was 67.6%. Factors associated with poorer maintenance were a higher Charlson comorbidity index (HR 1.311 (1.089-1.579); p = 0.0042), a higher age (HR 1.055 (1.015-1.096); p = 0.0067), and corticosteroids therapy at initiation (HR 2.722 (1.006-7.365); p = 0.0487). The clinical and biological safety profile was generally good. CONCLUSIONS: Our study found that a higher Charlson index, age, and corticosteroids appeared to be associated with the earlier discontinuation of treatment. JAKis had a response and tolerance profile in real life at least equivalent to that of biological disease-modifying antirheumatic drugs (bDMARDs).

Mobile Phone Text Messages and Effect on Treatment Adherence in Patients Taking Methotrexate for Rheumatoid Arthritis: A Randomized Pilot Study.

OBJECTIVE: To assess the impact of weekly text messages on adherence in patients taking methotrexate (MTX) for rheumatoid arthritis (RA). METHODS: This prospective, randomized pilot, single-site study included patients with RA stabilized using MTX alone or combined with biologics. Participants were randomized to 3 interventions: a standard consultation (controls), a 15-minute pharmacist-led counseling session, or the receipt of text message reminders. The change over time in the Compliance Questionnaire Rheumatology (CQR-19) score between baseline and 6 months was defined as the primary outcome for adherence. Multivariable analyses and final adherence (as a composite outcome of the CQR-19 score, the Girerd score, and the medication possession ratio) were probed in sensitivity tests. Rheumatologic scales, inflammation, and patient satisfaction were also analyzed. RESULTS: A total of 96 patients (mean ± SD Disease Activity Score in 28 joints 2.42 ± 1.03) were monitored. The change over time in the CQR-19 score was significantly higher in the text message group (mean ± SD 3.32 ± 5.66; P = 0.02) than in the control group (mean ± SD 0.22 ± 6.56) and the pharmacist-led counseling group (mean ± SD -0.14 ± 7.56). Multivariable logistic regression showed that text messages remained associated with an increase in the CQR-19 score, independently of the baseline CQR-19 score (odds ratio 3.63 [95% confidence interval 1.26-10.49]; P = 0.017). In the text message group, the increase in the CQR-19 score was correlated with the Health Assessment Questionnaire score (r = -0.405, P = 0.021), and patient satisfaction was significantly higher (P < 0.01) than in the control group. CONCLUSION: Our results showed evidence of a positive impact of text messages on adherence to MTX treatment for RA. The clinical benefit and the ideal target patient remain to be determined.

Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study.

BACKGROUND: Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy. METHODS: We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively. FINDINGS: Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 (n = 16) or cohort 2 (n = 16). The median (range) age was 64 (45-88). The tumor types were non-small-cell lung cancer (n = 15, 47%), melanoma (n = 6, 19%), renal carcinoma (n = 3, 9%), and other malignancies (n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1-2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1. INTERPRETATION: Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.

Osteoarticular side effects of BCG therapy.

Although osteoarticular side effects of the Bacillus Calmette-Guérin (BCG) are rare compared to the number of administrations, BCG vaccination and cancer therapy are so widely used that the absolute number of cases is not negligible. Osteoarticular infection is an exceedingly rare complication of vaccination with the BCG. Intravesical BCG instillations used to treat superficial bladder cancer may cause arthralgia, reactive arthritis or osteoarticular infections. Intradermal BCG therapy used to treat a number of malignancies can cause osteoarticular infections or bilateral symmetric polyarthritis predominating in the wrists and fingers. In practice, when intravesical BCG instillation is followed by arthritis, hyperthermia is unhelpful for distinguishing septic arthritis from reactive arthritis. Arguments pointing to reactive arthritis include oligo- or polyarticular involvement and onset a few weeks (as opposed to a few months) after the last instillation. Nevertheless, joint fluid examination is in order to rule out septic arthritis. BCG-induced reactive arthritis usually responds well to nonsteroidal anti-inflammatory drugs. Osteoarticular infections related to BCG therapy should be treated by rifampin, isoniazid and ethambutol for 2 months, followed by rifampin and isoniazid for 10 months.

Clinical and laboratory safety of one year's use of a combination calcium + vitamin D tablet in ambulatory elderly women with vitamin D insufficiency: results of a multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: This article presents the results of an evaluation of the clinical and laboratory safety of a 1-year course of treatment with a combination calcium and vitamin D tablet in ambulatory women aged >65 years with vitamin D insufficiency. METHODS: In a multicenter, randomized, double-blind, placebo-controlled study conducted in France, women with a 25-hydroxyvitamin D level < or =12 ng/mL were randomized to receive either a combination tablet containing calcium carbonate 500 mg and vitamin D3 400 IU taken twice daily or a matching placebo tablet for 1 year. A complete clinical examination was performed at baseline and at 3, 6, 9, and 12 months of treatment; blood and urine samples were collected for laboratory analyses at the same time points. Safety was monitored based on adverse events recorded during the treatment period and on the results of laboratory tests, including measurement of creatinine and uric acid levels. RESULTS: The study included 192 women (mean [SD] age, 74.6 [6.9] years; mean weight, 64.0 [12.5] kg), 95 in the calcium + vitamin D group and 97 in the placebo group. Fifty women (21/95 [22.1%] calcium + vitamin D, 29/96 [30.2%] placebo) were prematurely withdrawn from the study for various reasons, with no difference in withdrawals between groups. Treatment-related adverse events were reported in 21 (22.1%) and 23 (24.0%) women in the respective treatment groups. These events consisted mainly of metabolic disorders (9 [9.5%] and 10 [10.4%], respectively), particularly hypercalcemia (6 [6.3%] and 8 [8.3%]) and gastrointestinal disorders (9 [9.5%] and 8 [8.3%]). No major complications directly related to calcium and vitamin D supplementation occurred during the course of treatment. Although renal function was not altered, the group who received calcium + vitamin D had significantly elevated concentrations of serum uric acid compared with those who received placebo (52.3% vs 37.2%; P = 0.046) but not urinary uric acid. CONCLUSIONS: In these ambulatory elderly women with vitamin D deficiency, supplementation with calcium + vitamin D appeared to be well tolerated over 1 year of treatment. No significant effects on creatinine clearance were observed. However, the proportion of women with elevated serum uric acid concentrations was significantly greater in those who received calcium + vitamin D compared with those who received placebo.

Prediction of bone mass density variation by bone remodeling markers in postmenopausal women with vitamin D insufficiency treated with calcium and vitamin D supplementation.

The aim of this study was to determine whether early changes in bone markers could predict long-term response in bone mineral density (BMD) after calcium (500 mg) and vitamin D (400 IU) supplementation twice daily in ambulatory elderly women with vitamin D insufficiency (25-hydroxyvitamin D, <12 ng/ml). One hundred and ninety-two women (mean age, 75 +/- 7 yr) were randomized to receive either the supplementation (n = 95) or a placebo (n = 97) in a double-blind, controlled clinical trial for 1 yr. In comparison with the placebo group, supplementation significantly increased BMD, normalized 25-hydroxyvitamin D and significantly decreased intact PTH and bone remodeling markers. The initial values of telopeptide cross-links were correlated with improvement in total body BMD [urinary N-telopeptides (NTX), r = 0.38; C-telopeptides (CTX), r = 0.32; serum CTX, r = 0.28], and the 3-month changes in the same markers were correlated with improvement in total body (urinary N-telopeptides, r = -0.29; serum CTX, r = -0.26) and vertebral BMD (CTX, r = -0.26; all P < 0.05). We concluded that short-term changes in bone resorption markers can predict long-term variations in BMD in elderly women with vitamin D insufficiency receiving calcium and vitamin D supplementation.

Longitudinal femoral shaft due to bone insufficiency. A review of three cases.

We report three new cases of longitudinal femoral shaft fracture due to bone insufficiency and review the eight cases reported in the literature. The typical patient is a woman older than 65 years of age who present with mechanical pain in the thigh and/or groin. Palpation of the thigh may reproduce the pain. The diagnosis is often made late because the radiographs are normal initially. However, an early and consistent finding is increased radionuclide uptake along the femoral shaft. The fracture line is readily evidenced by computed tomography but may be difficult to see on magnetic resonance imaging. Use of crutches for 6 weeks to protect the bone from weight bearing ensures healing of the fracture.

Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency.

OBJECTIVE: Calcium and vitamin D deficiency is common in older individuals, particularly those who live in nursing homes, and increases the risk of osteoporosis and fractures. METHODS: We conducted a randomized double-blind placebo-controlled study of combined supplementation with 500 mg of elemental calcium, as carbonate, and 400 IU of vitamin D bid for 12 months in women older than 65 years of age with vitamin D deficiency, defined as serum 25(OH)D concentrations

Treatment persistence and changes in fracture risk, back pain, and quality of life amongst patients treated with teriparatide in routine clinical care in France: results from the European Forsteo Observational Study.

OBJECTIVES: The European Forsteo Observational Study assessed the clinical fracture incidence, back pain, quality of life (QoL), and treatment persistence amongst post-menopausal women, who were prescribed teriparatide in routine care in eight European countries. We present the results for France, with health-insurance reimbursement criteria channel teriparatide to women with severe disease and limit treatment to 18 months. METHODS: A representative sample of women initiating teriparatide in France was followed in routine care for 36 months. We described patients' characteristics at baseline and persistence to teriparatide (Kaplan-Meier analysis), fracture incidence, back pain, and QoL (EQ-5D) at baseline, 18 and 36 months follow-up (last-observation-carried-forward (LOCF) and mixed-models-for-repeated-measures (MMRM). RESULTS: One hundred and sixteen rheumatologists included 309 patients, of whom 290 (93.9%) had at least one follow-up visit. Women's mean age (standard deviation) was 74.5 years (7.4) and 296 (95.8%) had greater or equal to two vertebral fractures prior to teriparatide initiation. Clinical fracture incidence, mainly vertebral fractures, decreased around 6 months after teriparatide initiation, and was sustained at 36 months (P=0.013) when most patients were treated by anti-resorptives. Back pain and EQ-5D measures improved significantly at 18 and 36 months (P<0.0001) in the LOCF analyses but did not improve in the EQ-5D VAS measure after covariate adjustment in the MMRM model. Median treatment duration was 17.4 months. CONCLUSION: French women initiating teriparatide in routine care had severe osteoporosis and showed good treatment persistence, consistent with France's insurance reimbursement criteria. Improvements in fracture risk and back pain began soon after treatment and was maintained at 36 months follow-up.

Difficulties in the diagnosis of vertebral fracture in men: agreement between doctors.

UNLABELLED: The agreement for vertebral fracture (VF) diagnosis in men, between doctors is poor. OBJECTIVES: To assess the agreement for VF diagnosis, in men, on standard radiographs, between experts, before and after consensual workshop and establishing an algorithm. METHODS: The agreement between thirteen experimented rheumatologists has been calculated in thirty osteoporotic men. Then, the group discussed in a workshop and 28 other radiograph sets of osteoporotic men with follow-up radiographs and incident confirmed VF, have been reviewed. The experts identified and hierarchised 18 pathological features of vertebral deformation and established an algorithm of VF diagnosis. Eleven experts have realized a second reading of the first set of radiographs. We compared the agreement between the 2 readings without and with the algorithm. RESULTS: After consensus and the use of the algorithm the results are: number of fractured patients (with at least 1 VF) according to the experts varies from 13 to 26 patients out of 30 (13 to 28 during the first reading). The agreement between the experts at the patient level is 75% (70% at the first reading). Among the 390 vertebrae analyzed by the experts, the number of VF detected varies from 18 to 59 (18 to 98 at the first reading). The agreement between the experts at the vertebral level is 92% (89% at the first reading). The algorithm allows a good improvement of the agreement, especially for 8 of the 11 experts. Discrepancies for the VF diagnosis between experts exist. The algorithm improves the agreement.

Musculoskeletal ultrasonography in healthy subjects and ultrasound criteria for early arthritis (the ESPOIR cohort).

OBJECTIVE: To confirm the occurrence of bone erosions and synovitis in healthy subjects detectable by ultrasound (US) and to establish US criteria for early arthritis. METHODS: Our study involved 127 healthy subjects matched with a cohort of patients with early arthritis (the ESPOIR cohort). The second and fifth metacarpophalangeal (MCP) joints and the fifth metatarsophalangeal (MTP) joint of both hands and feet were assessed with US to detect bone erosion; and the second, third, fourth, and fifth MCP and the fifth MTP were evaluated for synovial thickening in B-mode US and synovial vascularity in power Doppler. Bone erosion and synovitis were defined according to the Outcome Measures in Rheumatology Clinical Trials consensus. RESULTS: Bone erosion and grade 2-3 synovial thickening in B-mode were detected in 11% and 9% of healthy subjects. To consider the diagnosis of early arthritis, a cutoff at 1 case of synovial thickening in B-mode enabled discrimination between patients with early arthritis and healthy subjects, with a good sensitivity of 74.8% (95% CI 67.2%-82.3%) and a high specificity of 90.5% (95% CI 85.4%-95.6%). If higher specificity is required to confirm the diagnosis of early arthritis, cutoff at 2 cases of synovial thickening in B-mode or at 2 cases of bone erosion gave optimal results, with specificity of 98.4% (95% CI 96.2%-100%) and 100%, respectively, and lower sensitivity of 59.8% (95% CI 51.2%-68.3%) and 17% (95% CI 10.5%-23.5%) (area under the curve = 0.85 for synovitis and 0.63 for bone erosion). Neither the combination of power Doppler signal plus bone erosion, nor bone erosions plus synovial thickening on the same joint, were seen in healthy subjects. CONCLUSION: A single case of bone erosion or synovial thickening in B-mode is common in healthy subjects. However, more than 1 case of synovial thickening in B-mode or bone erosion is a strong argument for the diagnosis of early inflammatory arthritis.

First case of human spondylodiscitis due to Shewanella algae.

We present the first case of human spondylodiscitis due to Shewanella algae. Our patient did not have any predisposing factors. The portal of entry was probably a cutaneous lesion on the leg, exposed to seawater. Bacteria were isolated in pure culture from a needle biopsy specimen of the vertebral disk. Automated identification systems identified the organism as Shewanella putrefaciens. However, molecular biology identified it as S. algae. Treatment with ceftriaxone and amikacin, then ciprofloxacin successfully addressed the infection. We also review four published cases of human osteoarticular infections caused by Shewanella spp: two cases of arthritis and two cases of osteomyelitis. Two patients had predisposing factors, and contact with water was found in two cases. The clinical, radiological and biological characteristics of S. algae spondylodiscitis are indistinguishable from those of spondylodiscitis of other causes. A cutaneous lesion with exposure to water is a potential portal of entry. Molecular typing is necessary to obtain a precise bacteriological identification.

Hematogenous Staphylococcus aureus discitis in adults can start outside the vertebral body.

BACKGROUND: Textbooks describe hematogenous discitis in adults as starting in the anterior vertebral body near the endplates. CASE REPORT: Hematogenous Staphylococcus aureus discitis developed at L1-L2 in an 81-year-old woman. On the first magnetic resonance imaging (MRI) scan performed 4 days after symptom onset, the only abnormalities were high signal from the disk on T2-weighted images, gadolinium enhancement of the soft tissues anterior to L1-L2, and epidural involvement. The endplates and vertebral bodies were normal. A subsequent MRI scan showed features typical of infectious discitis. DISCUSSION: We found a single similar case report in the medical literature, indicating that discitis starting outside the anterior vertebral body is rare. Nevertheless, an increasing number of similar cases may be diagnosed in the future, as MRI is being performed increasingly early in patients with a clinical suspicion of infectious discitis. CONCLUSION: Hematogenous infectious discitis in adults may start in some patients within the disk, soft tissues anterior to the disk, or epidural space. To avoid diagnostic and therapeutic delays, physicians should be aware of this unusual presentation of infectious discitis on very early MRI scans. When the clinical picture suggests discitis and findings from the early MRI scan are atypical, a repeat MRI scan should be obtained 1 week later to confirm the diagnosis.