Management and outcome of native joint septic arthritis: a nationwide survey in French rheumatology departments, 2016-2017.

OBJECTIVES: To describe current management and outcome of native joint septic arthritis (NJSA) in French rheumatology departments. METHODS: For this retrospective, nationwide multicentric study, 127 French rheumatology departments were contacted to report up to 12 cases of NJSA that occurred between 1 January 2016 and 31 December 2017. Characteristics, diagnosis procedures, therapeutic management and outcome were recorded. RESULTS: Overall, 362 patients were included (mean age 64.0±18.6 years, median Charlson comorbidity index 3.5 (0-14)). Knee was the most frequent site (n=160 (38.9%)), and Staphylococcus sp (n=185 (51.4%)), the most frequent pathogen. All patients received antibiotics for a mean duration of 46.8 (±22.0) days, including intravenous route for a mean of 17.2 (±15.4) days. Management was heterogeneous. Surgical procedure was performed in 171 (48.3%), joint immobilisation in 128 (43.8%). During follow-up, 91 (28.3%) patients have had serious complications and 28 (9.2%) of them died. Factors associated with 1-year mortality were age (OR 1.08, 95% CI 1.04 to 1.13; p<0.001), Charlson's index (OR 1.30, 95% CI 1.06 to 1.58; p=0.012), presence of bacteraemia (OR 4.02, 95% CI 1.35 to 11.99; p=0.008), antibiotic use in the previous 3 months (OR 3.32, 95% CI 1.11 to 9.87; p=0.029) and Staphylococcus aureus NJSA compared with Streptococcus sp. NJSA (OR 7.24, 95% CI 1.26 to 41.68, p=0.027). The complete recovery with no adverse joint outcome at 1 year was observed in n=125/278 patients (55.0%). CONCLUSION: Prognosis of NJSA remained severe with a high rate of morbimortality. Its management was very heterogeneous. This study highlights the importance of the new French recommendations, published after the completion of the study, in order to facilitate NJSA management.

Clinical characteristics and management of olecranon and prepatellar septic bursitis in a multicentre study.

BACKGROUND: No current guidelines are available for managing septic bursitis (SB). OBJECTIVES: To describe the clinical characteristics and management of olecranon and prepatellar SB in five French tertiary care centres. METHODS: This is a retrospective observational multicentre study. SB was diagnosed on the basis of positive cultures of bursal aspirate. In the absence of positive bursal fluid, the diagnosis came from typical clinical presentation, exclusion of other causes of bursitis and favourable response to antibiotic therapy. RESULTS: We included 272 patients (median age of 53 years, 85.3% male and 22.8% with at least one comorbidity). A microorganism was identified in 184 patients (67.6%), from bursal fluids in all but 4. We identified staphylococci in 135 samples (73.4%), streptococci in 35 (19%) and 10 (5.5%) were polymicrobial, while 43/223 bursal samples remained sterile (19.3%). Forty-nine patients (18%) were managed without bursal fluid analysis. Antibiotic treatment was initially administered IV in 41% and this route was preferred in case of fever (P = 0.003) or extensive cellulitis (P = 0.002). Seventy-one (26%) patients were treated surgically. A low failure rate was observed (n = 16/272, 5.9%) and failures were more frequent when the antibiotic therapy lasted <14 days (P = 0.02) in both surgically and medically treated patients. CONCLUSIONS: Despite variable treatments, SB resolved in the majority of cases even when the treatment was exclusively medical. The success rate was equivalent in the non-surgical and the surgical management groups. However, a treatment duration of <14 days may require special attention in both groups.

Ruling out septic arthritis risk in a few minutes using mid-infrared spectroscopy in synovial fluids.

OBJECTIVES: The aim of this study was to show the usefulness of a mid-infrared fibre evanescent wave spectroscopy point of care device in the identification of septic arthritis patients in a multicentre cohort, and to apply this technology to clinical practice among physicians. METHODS: SF samples from 402 patients enrolled in a multicentre cohort were frozen for analysis by mid-infrared fibre evanescent wave spectroscopy. The calibration cohort was divided into two groups of patients (septic arthritis and non-septic arthritis) and relevant spectral variables were used for logistic regression model. Model performances were tested on an independent set of 86 freshly obtained SF samples from patients enrolled in a single-centre acute arthritis cohort and spectroscopic analyses performed at the patient's bedside. RESULTS: The model set-up, using frozen-thawed SFs, provided good performances, with area under the curve 0.95, sensitivity 0.90, specificity 0.90, positive predictive value 0.41 and negative predictive value 0.99. Performances obtained in the validation cohort were area under the curve 0.90, sensitivity 0.92, specificity 0.81, positive predictive value 0.46 and negative predictive value 0.98. The septic arthritis probability has been translated into a risk score from 0 to 4 according to septic risk. For a risk score of 0, the probability of identifying a septic patient is very low (negative predictive value of 1), whereas a risk score of 4 indicates very high risk of septic arthritis (positive predictive value of 1). CONCLUSION: Mid-infrared fibre evanescent wave spectroscopy could distinguish septic from non-septic synovial arthritis fluids with good performances, and showed particular usefulness in ruling out septic arthritis. Our data supports the possibility of technology transfer. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02860871.

IL-26 is overexpressed in rheumatoid arthritis and induces proinflammatory cytokine production and Th17 cell generation.

Interleukin-26 (IL-26), a member of the IL-10 cytokine family, induces the production of proinflammatory cytokines by epithelial cells. IL-26 has been also reported overexpressed in Crohn's disease, suggesting that it may be involved in the physiopathology of chronic inflammatory disorders. Here, we have analyzed the expression and role of IL-26 in rheumatoid arthritis (RA), a chronic inflammatory disorder characterized by joint synovial inflammation. We report that the concentrations of IL-26 are higher in the serums of RA patients than of healthy subjects and dramatically elevated in RA synovial fluids compared to RA serums. Immunohistochemistry reveals that synoviolin(+) fibroblast-like synoviocytes and CD68(+) macrophage-like synoviocytes are the main IL-26-producing cells in RA joints. Fibroblast-like synoviocytes from RA patients constitutively produce IL-26 and this production is upregulated by IL-1-beta and IL-17A. We have therefore investigated the role of IL-26 in the inflammatory process. Results show that IL-26 induces the production of the proinflammatory cytokines IL-1-beta, IL-6, and tumor necrosis factor (TNF)-alpha by human monocytes and also upregulates the expression of numerous chemokines (mainly CCL20). Interestingly, IL-26-stimulated monocytes selectively promote the generation of RORgamma t(+) Th17 cells, through IL-1-beta secretion by monocytes. More precisely, IL-26-stimulated monocytes switch non-Th17 committed (IL-23R(-) or CCR6(-) CD161(-)) CD4(+) memory T cells into Th17 cells. Finally, synovial fluids from RA patients also induce Th17 cell generation and this effect is reduced after IL-26 depletion. These findings show that IL-26 is constitutively produced by RA synoviocytes, induces proinflammatory cytokine secretion by myeloid cells, and favors Th17 cell generation. IL-26 thereby appears as a novel proinflammatory cytokine, located upstream of the proinflammatory cascade, that may constitute a promising target to treat RA and chronic inflammatory disorders.

Septic arthritis of the facet joint is also a severe vertebral infection: A multicenter retrospective study of 65 patients.

OBJECTIVE: Septic arthritis of the Facet Joints (SAFJ) is a rare condition. Little data has been published on the subject. We aimed to describe the clinical, biological and imagery presentations, as well as the course of this rare infection. METHODS: We included patients hospitalized between January 1st, 2016 and December 31th, 2019, in the Departments of Infectious Diseases or Rheumatology in 5 French centres in the CRIOGO network. We defined septic arthritis according to Newman's criteria and facet joint arthritis using imagery. RESULTS: Sixty-five patients were included, predominantly males (64.6%), with a mean age of 68.1 years. The mean time to diagnosis was 25.0 days. The principal symptoms at diagnosis were acute back pain (95.2%) and fever (76.9%). Neurological symptoms were present for 60.7% of the patients, including 16.4% motor deficit or cauda equina syndrome. SAFJ was located on the lumbosacral spine (73.4%) and was rarely multifocal (4.7%). Bacteriological identification was performed by blood cultures in 84.4% of the cases, and the pathogen was mainly Staphylococcus aureus (49.2%). Infective endocarditis was present for 26.9% of patients assessed by echocardiography. On MRI, soft tissue abscess or inflammation, epiduritis and epidural abscess were present in 87.1%, 66.7% and 33.9% of cases, and the pathogen was significantly more frequently Staphylococcus aureus. Mortality reached 9.2%, 18.5% and 23% at one, two, and three years respectively. CONCLUSION: SAFJ is a rare but severe disease. Microbiological diagnosis is primarily made on blood cultures, and S. Aureus was the main pathogen. Our results highlight the fact that SAFJ is associated with high morbidity and mortality, and with infective endocarditis.

Association between radiographic and functional outcome in vertebral osteomyelitis SPONDIMMO, a 6-month prospective multicenter cohort.

OBJECTIVES: This study aimed to describe radiographic and functional evolution over 6 months in a large cohort of VO patients. METHODS: We prospectively recruited patients with VO from 2016 to 2019 in 11 French centers. X-rays were performed at baseline, 3 months, and 6 months to assess progression using structural and static criteria. Functional impairment was evaluated using the Oswestry Disability Index (ODI) at 3 months and 6 months. RESULTS: Two hundred and twenty-two patients were included. Mean age was 67.8±14 years, mostly men (67.6%). After 3 months, there was a significant increase in vertebral fusion (16.4% vs 52.7%), destruction of vertebral bodies (10.1% vs 22.8%), and of all the static features (frontal angulation (15.2% vs 24.4%), segmental (34.6% vs 56%) and regional (24.5% vs 41%) kyphosis). From 3 to 6 months, among the different X-ray abnormalities, only the complete fusion progressed significantly (16.6% vs 27.2%). Median ODI showed significant improvement from 3 to 6 months (24, IQR [11.5-38] vs 16, IQR [6-34]). At 6 months, 14.1% of the patients had a severe disability, 2% a major disability. The persistence of vertebral destruction at 6 months was associated with a higher ODI (16, IQR [7.5-30.5] vs 27, IQR [11.5-44.5]). No differences in radiological progression were observed with immobilization using a rigid brace. CONCLUSION: Our study demonstrates structural and static radiographic progression after 3 months. Only the complete fusion progressed over the long-term. Functional impairment was associated with persistence of vertebral destruction.

[Osteoporosis in men]. / Ostéoporose chez l'homme.

Epidemiologic studies have shown that 25% of osteoporotic fractures occur in men. Their prognosis is poor with one third of deaths in the year following the proximal femur fracture. Screening is based on the analysis of risk factors (prolonged corticosteroid therapy, anti androgen, smoking or alcohol abuse, liver disease or chronic inflammatory diseases), taking into account fracture history and bone density measurement. The prescription of bisphosphonates or teriparatide must be preceded by an etiologic investigation, a withdrawal of bone loss-induced drugs (tobacco, alcohol, steroids), a recovery of walking and a specific action on fall risk, especially after 70 years.

Spine immobilization and neurological outcome in vertebral osteomyelitis SPONDIMMO, a prospective multicentric cohort.

OBJECTIVE: The aim of our study was to describe spine immobilization in a multicentric cohort of vertebral osteomyelitis (VO), and evaluate its association with neurological complications during follow-up. METHODS: We prospectively included patients from 2016 to 2019 in 11 centers. Immobilization, imaging, and neurological findings were specifically analyzed during a 6-month follow-up period. RESULTS: 250 patients were included, mostly men (67.2%, n=168). Mean age was 66.7±15 years. Diagnosis delay was 25 days. The lumbo-sacral spine was most frequently involved (56.4%). At diagnosis, 25.6% patients (n=64) had minor neurological signs and 9.2% (n=23) had major ones. Rigid bracing was prescribed for 63.5% (n=162) of patients, for a median of 6 weeks, with variability between centers (P<0.001). The presence of epidural inflammation and abscess on imaging was associated with higher rates of rigid bracing prescription (OR 2.33, P=0.01). Frailness and endocarditis were negatively associated with rigid bracing prescription (OR 0.65, P<0.01, and OR 0.42, P<0.05, respectively). During follow up, new minor or major neurological complications occurred in respectively 9.2% (n=23) and 6.8% (n=17) of patients, with similar distribution between immobilized and non-immobilized patients. CONCLUSION: Spine immobilization prescription during VO remains heterogeneous and seems associated inflammatory lesions on imaging but negatively associated with frailness and presence of endocarditis. Neurological complications can occur despite rigid bracing. Our data suggest that in absence of any factor associated with neurological complication spine bracing might not be systematically indicated. We suggest that spine immobilization should be discussed for each patient after carefully evaluating their clinical signs and imaging findings.

A rare case of Prosthetic Joint Infection associated with Coxiella burnetii.

We report here the case of a Prosthetic Joint Infection (PJI) associated with Coxiella burnetii in a 62-year-old man with a revised total hip arthroplasty. The diagnosis was performed first by 16S rDNA sequencing on hip fluid aspirate, and confirmed by specific qPCR. Q fever has been reported in few cases of Prosthetic Joint Infections, often associated with chronic evolution and iterative surgeries. This case report alerts about such an unexpected diagnosis in a patient with no known risk factors.

[Disc herniation-induced sciatica: medical or surgical treatment?]. / Conduite à tenir devant une lomboradiculalgie.

Radiculopathy is a common condition, characterized by a spontaneous regression: in 95 percent of patients, it resolves without surgery, within 1 to 12 months. To shorten the course of this disease, enable patients to resume social and professional activities and avoid chronicity, several therapeutic solutions have been assessed. Based on scientific evidence supporting effectiveness, physicians may prescribe analgesics, NSAID and epidural infiltrations, which probably relieve the pain and improve the quality of life without really modifying the mid-term prognosis. Following a specialized physical, social and professional assessment, surgery may be offered to patients who keep experiencing radicular (and not lumbar) pain. The complication rate is approximately 1 to 3 percent. The effectiveness of surgery is well established, especially with an improved recovery time (50 percent as compared to medical treatment). However, the superiority of a particular surgical technique has not been demonstrated. To date, we are still lacking evidence to demonstrate the effectiveness of percutaneous techniques in good methodological conditions. Finally, confinement to bed, cortisone administered per os or IV, localized spinal manipulations, corsets, vertebral tractions and physiotherapy have no demonstrated impact on the course of sciatica.

Isolated vasculitis of the female genital tract: a case series and review of literature.

To provide a clinicopathologic review of vasculitis confined to the female genital tract, we describe three cases, and we searched PubMed from 1965 to 2006 with analysis of all relevant articles. We identified 118 additional cases in the literature of whom 108 had isolated necrotizing vasculitis similar to classical polyarteritis nodosa (PAN-type), and 10 presented isolated giant cell arteritis (GCA-type) of the female genital tract. In most cases, arteritis was discovered surprisingly. The mean age of these patients was 48.6 years for the PAN-type and 64.1 for the GCA-type. Vasculitis affected a single organ in 88 (81.5%) cases of which 71 (65.7%) involved the cervix in the PAN-type, whereas it was limited in the myometrium in five (50%) cases in the GCA-type. There was no progression to a systemic vasculitis in 99.1% of the cases. A comparable favorable outcome was reported after surgery in all cases with a mean follow-up of 40.8 months. We conclude that isolated vasculitis of the female genital tract is a distinct condition, with two different patterns but a similar favorable outcome after resection. Its knowledge is needed to avoid aggressive evaluation and therapy.

Early arterial calcification does not correlate with bone loss in pseudoxanthoma elasticum.

BACKGROUND AND AIMS: Pseudoxanthoma elasticum (PXE; OMIM 264800, prevalence 1/25,000 to 1/50,000) is an autosomal recessive multisystem disease due to deficiency in ABCC6, an ATP-binding cassette, sub-family C transporter. The PXE phenotype is mainly characterized by progressive ectopic calcification of connective tissues (namely skin, retinal Bruch's membrane and peripheral arteries) but the impact of PXE on bone structure is currently unknown. The present study sought to investigate bone mineralization and its potential link with vascular calcification in a large cohort of PXE patients with inherited mutations of the ABCC6 gene. METHODS AND RESULTS: 96 patients (61 women) matching the PXE criteria participated in this study. Their clinical history and status and bone biological markers were collected. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry and expressed as T- and Z-scores. Osteoporotic fractures were identified by X-ray, and coronary (CAC) and lower limb arterial calcification (LLAC) scores were determined by CT scan. RESULTS: 44% of the women were menopausal. Osteopenia was disclosed in 46% (17 women) while 23% (9 women) exhibited osteoporosis, 3 with severe osteoporosis. Fractures of an osteoporotic nature were authenticated in 3 patients (1 woman). Markers of bone remodelling processes (CTX, BSAP and osteocalcin) were within the normal range for our laboratory standards. Severe vitamin D deficiency (<25nmol/L) was found in 15%, while 51% exhibited no vitamin D deficiency (vitamin D≥50nmol/L). LLAC and CAC scores were significantly higher in the patients with a low T- and/or Z-score, although this difference disappeared in multivariate analysis with age as a confounding factor. There was no significant difference in LLAC and CAC between PXE patients with and without osteoporotic fractures. There was no statistically significant association between BMD, LLAC and CAC and any of the bone remodelling factors. CONCLUSIONS: This is the first report on the bone mineralization process in PXE patients. Our data shows that PXE patients are not markedly prone to exaggerated bone demineralization and fracture risk, and prevalence of osteoporosis remains within the normal range for the general population. Furthermore, the relationships between LLAC, but not CAC, and BMD with age are similar to those observed in the general population. Therefore, despite its pivotal role in ectopic calcification, ABCC6 deficiency does not interfere with the bone-vascular axis. The lack of PXE-related disturbances between BMD and arterial calcification also supports vitamin D supplementation in PXE patients with vitamin D deficiency. ClinicalTrials.gov Identifier: NCT01446393.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS): definition, semiology, prognosis, pathogenesis, treatment, and place relative to other periodic joint diseases.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant inherited condition of periodic fever and pain. Most patients are of northern European descent. The attacks manifest as fever and pain in the joints, abdomen, muscles, skin, or eyes, with variations across patients. An acute-phase response occurs during the attacks. Patients with TRAPS are at risk for AA amyloidosis, the most common targets being the kidneys and liver. Soluble TNFRSF1A is usually low between the attacks and may be normal during the attacks, when TNF levels are high. TNFRSF1A is found in abnormally high numbers on leukocyte cell membranes. TRAPS is the first condition for which naturally occurring mutations in a TNF receptor were found; the mutations affect the soluble TNFRSF1A gene in the 12p13 region. In some patients, the pathogenesis involves defective TNFRSF1A shedding from cell membranes in response to a given stimulus. Thus, TRAPS is a model for a novel pathogenic concept characterized by failure to shed a cytokine receptor. This review compares TRAPS to other inherited periodic febrile conditions, namely, familial Mediterranean fever, Muckle-Wells syndrome, cold urticaria, and hyper-IgD syndrome. The place of TRAPS relative to other intermittent systemic joint diseases is discussed. Colchicine neither relieves nor prevents the attacks, whereas oral glucocorticoid therapy is effective when used in dosages greater than 20 mg/day. The pathogenic hypothesis involving defective TNFRSF1A shedding suggests that medications targeting TNF may be effective in TRAPS.

Is androgen therapy indicated in men with osteoporosis?

Male osteoporosis is not rare, and its management is a public health issue. The clinical evaluation must include investigations for one or more etiological factors such as hypogonadism, which is found in 5% to 15% of men with osteoporosis. Gradual development of moderate hypogonadism is the most common situation, and the prevalence of hypogonadism increases with advancing age. The wealth of scientific data establishing a major role for sex hormones in growth, bone turnover, and the osteoporotic fracture risk is in striking contrast to the paucity of therapeutic trials. Androgen therapy did not consistently produce bone mass gains, and no data on potential anti-fracture effects are available. Androgen therapy was not associated with significant increases in mortality, prostate disorders, or cardiovascular events, but few data were obtained in patients older than 75 years. In practice, in a male patient with osteoporosis, a diagnosis of marked and persistent hypogonadism requires investigations for treatable causes. In patients younger than 75 years of age, androgen replacement therapy should be started, in collaboration with an endocrinologist. A history of fractures indicates a need for additional osteoporosis pharmacotherapy. The risk/benefit ratio of androgen therapy is unclear in men older than 75 years, in whom a reasonable option consists in combining fall-prevention measures, vitamin D supplementation, and a medication proven to decrease the risk of proximal femoral fractures.

Rheumatic and musculoskeletal features of Whipple disease: a report of 29 cases.

OBJECTIVE: Whipple disease is a rare infection caused by Tropheryma whipplei. Although patients commonly complain of osteoarticular involvement, musculoskeletal manifestations have been poorly described. We report cases of Whipple disease with rheumatic symptoms and describe their clinical presentation, modes of diagnosis, and outcomes. METHODS: This retrospective multicenter study included patients with Whipple disease diagnosed and referenced between 1977 and 2011 in 10 rheumatology centers in France and Italy. RESULTS: Twenty-nine patients were included. The median age was 55 years. The median time to diagnosis from first symptoms was 5 years. Polyarthritis was the most frequent presentation (20/29), and was most often chronic, intermittent (19/29), seronegative (22/23), and nonerosive (22/29). In all cases, the symptoms had led to incorrect diagnosis of inflammatory rheumatic disease and immunosuppressants, including biotherapy, were prescribed in most cases (24/29) without success. The diagnosis of Whipple disease was made by histological analysis, molecular biology tests, or both in 21%, 36%, and 43% of the cases, respectively. Duodenal biopsies were performed in most cases (86%). Synovial biopsies were performed in 18% of cases, but all contributed to diagnosis. The clinical outcomes after antibiotic therapy were good for all patients. CONCLUSION: Polyarthritis is the main feature observed in cases of Whipple disease; it is seronegative and associated with general and gastrointestinal symptoms. The molecular analysis of duodenal tissue and/or other tissues remains the method of choice to confirm the diagnosis. Reducing the time to diagnosis is important because severe late systemic and fatal forms of the disease may occur.

Sex hormone-binding globulin in osteoporosis.

Sex hormone-binding globulin (SHBG) is a plasma glycoprotein that binds with high affinity to sex steroids, most notably 5alpha-dihydrotestosterone, testosterone, and 17beta-estradiol, thereby regulating their bioavailability and access to target cells. SHBG modulates the sex-steroid signaling system by binding to a specific membrane receptor (SHBG-R). Plasma SHBG levels vary in health and disease due to the effects of multiple regulation factors (age, body weight, sex steroids, insulin, and others). SHBG is involved in a number of diseases, including osteoporosis. Several studies found an inverse correlation between serum SHBG levels and bone mineral density in both males and females. SHBG levels may predict a number of macro-architectural characteristics of cortical bone. Weaker links have been reported between SHBG and bone turnover markers. Finally, high SHBG levels predict the occurrence of osteoporotic fractures of the vertebras and peripheral bones, most notably the proximal femur. Together with estradiol, SHBG plays a key role in the genesis of bone loss and osteoporotic fractures. Given that serum SHBG elevation is associated with the occurrence of multiple fractures, determination of the serum SHBG level, which can be readily performed in everyday clinical practice, may constitute a useful new marker for predicting the severity of osteoporosis.

Monoclonal gammopathy of undetermined significance, multiple myeloma, and osteoporosis.

The finding of monoclonal gammopathy of undetermined significance (MGUS) is not infrequent during an evaluation for osteoporosis or a fracture. In most cases, the diagnosis is MGUS, whose prevalence increases with age. Although the impact of MGUS on bone mineral density, bone remodeling, and the fracture risk remains unclear, this asymptomatic hematological disorder may constitute a risk factor for osteoporosis. Furthermore, each year, 1% of patients with MGUS progress to multiple myeloma, a disease whose pathophysiology and association with bone loss and pathological fractures are increasingly well understood. Osteoporotic fractures, although probably common in myeloma patients, are less likely to be recognized. Here, we discuss the pathophysiology of myeloma and MGUS and their impact in terms of bone mineral density, osteoporotic fractures, and bone turnover markers.