Value of ultrasound-guided synovial biopsy for the diagnosis of infectious arthritis.

Objectives: To determine the value of ultrasound (US)-guided synovial biopsy for the diagnosis of infectious arthritis that could not be detected by other modalities. Material and methods: This descriptive study was conducted among 37 patients with arthritis (3 with shoulder arthritis, 2 with elbow arthritis, 7 with wrist arthritis, 15 with hip arthritis, 4 with knee arthritis, and 5 with ankle arthritis) who underwent US-guided synovial biopsy at Hanoi Medical University Hospital for the diagnosis of infec-tious arthritis that could not be detected by infection laboratory tests, imaging, and/or joint fluid culture. The results of US-guided synovial biopsy were positive for infectious arthritis when those of pathologi-cal analyses, bacterial cultures, and/or polymerase chain reaction test for tuberculosis were positive. The final diagnosis established when the patients were discharged from the hospital was compared with the US-guided synovial biopsy results to calculate the sensitivity and specificity for the diagnosis of infectious arthritis. Results: The median age of the patients was 60 years (range: 22-79 years), and two thirds were women. Infectious arthritis was determined as the final diagnosis in 18 patients. There was no significant difference in the infection laboratory test results, synovial thickness, or magnetic resonance imaging features apart from soft tissue abscess between the infectious and non-infectious arthritis groups (P > 0.05). The US-guided synovial biopsy results were positive in 17 patients. Compared with the sensitivity and specificity of the final diagnosis, those of the US-guided synovial biopsy results for the diagnosis of infectious arthritis were 94.4% and 100%, respectively. The Numerical Rating Scale score was ≤3 in most patients. There were neither vascular nor neurologic complications among the patients. Conclusion: Imaging features and laboratory test results are non-specific for infectious arthritis. US-guided synovial biopsy is a well-tolerated, safe method that has a high value for the diagnosis of infectious arthritis. This modality should then be recommended for patients with unclassified arthritis.

[Septic arthritis and transient synovitis of the hip]. / Septische Arthritis und Coxitis fugax.

CLINICAL/METHODICAL ISSUE: Differentiating between septic arthritis and transient synovitis can be challenging but is very important as a late diagnosis of septic arthritis can lead to sepsis and joint damage. For correct diagnosis and prediction of complications, the right combination of physical examination, laboratory and radiological studies is needed. STANDARD RADIOLOGICAL METHODS: Hip ultrasound is easy to learn and has a high sensitivity for joint effusion. Faster diagnosis and therapy are possible due to increasing use of ultrasound. Magnetic resonance imaging (MRI) is primarily used to rule out co-infections (osteomyelitis, pyomyositis) and differential diagnoses. X­ray is typically nonremarkable in septic arthritis. PRACTICAL RECOMMENDATIONS: Routine use of ultrasound in nontraumatic pediatric hip pain. Generous use of MRI in case of elevated inflammatory markers or inconclusive clinical findings. Using only few sequences may be appropriate to avoid sedation, primarily fluid sensitive sequences (fat-saturated T2, TIRM, STIR), in case of positive findings, accompanied by T1-weighted images.

Simultaneous neutralization of TGF-ß and IL-6 attenuates Staphylococcus aureus-induced arthritic inflammation through differential modulation of splenic and synovial macrophages.

Septic arthritis is a joint disease caused by Staphylococcus aureus. Different macrophage populations contribute in various ways to control blood-borne infections and induce inflammatory responses. Macrophage tissue-resident niche is necessary for the suppression of chronic inflammation and may contribute to the pathogenesis of septic arthritis. Thus, to obtain a resolution of the disease and restoration of synovial homeostasis, it needs the activation of macrophages that further regulate the inflammatory consequences. The aim of this study was to find out the mechanism by which neutralization of transforming growth factor-beta (TGF-ß) and/or interleukin (IL)-6 after induction of septic arthritis could alter the specific macrophage responses in spleen and synovial joints via different cytokines (osteoprotegerin (OPG), osteopontin (OPN), IL-10, IL-12 and CXCL8) cross-talking, and how the response could be modulated by reactive oxygen species vs antioxidant enzyme activities. Dual neutralization of TGF-ß and IL-6 is notably effective in eliciting splenic and synovial tissue-resident macrophage responses. Synovial macrophage-derived IL-10 can elicit protection against septic arthritis via regulating receptor-activated nuclear factor Kappa-B ligand (RANKL)/OPG interaction. They also reduced oxidative stress by increasing the activity of antioxidant enzymes including SOD and catalase. Histopathological analysis revealed that dual neutralization of TGF-ß and IL-6 prevented bone destruction and osteoclastic activity in septic arthritis by promoting the differential functional response of the splenic and synovial macrophages. Additionally, the macrophage-derived IL-10 can elicit protection against S. aureus-induced septic arthritis via regulating RANKL/OPG interaction. Further studies on STAT3 and STAT4 are needed for the understanding of such cross-talking in resident macrophages of arthritic mice.

CT diagnosis of pituitary abscess, suppurative meningitis, and atlanto-occipital septic arthritis in a pony.

A 15-year-old pony was presented for acute neurological signs. Neurological examination suggested a brainstem lesion, blood laboratory tests detected an active inflammatory process, and upper respiratory endoscopy identified a suppurative lesion at the dorsal aspect of the right guttural pouch. Computed tomography was performed and findings were consistent with pituitary abscess, meningitis, and atlanto-occipital joint septic arthritis. Imaging findings were confirmed based on cerebrospinal and synovial fluid cultures and necropsy. Computed tomography provided important information for identifying the cause of the patient's neurological signs and helped the owner make a final decision for euthanasia.

Fermentation supernatant of Staphylococcus aureus drives catabolism in chondrocytes via NF-κB signaling mediated increase of cholesterol metabolism.

Septic arthritis induced by Staphylococcus aureus (S. aureus) causes irreversible cartilage degradation and subsequent permanent joint dysfunction. Recently, cartilage degradation in osteoarthritis is recognized to be associated with metabolic disorders. However, whether cholesterol metabolism is linked to septic arthritis pathology remains largely unknown. Here, we found that exposure to fermentation supernatant (FS) of S. aureus in chondrocytes resulted in a significant increase in expression of key modulators involved in cholesterol metabolism, including lectin-type oxidized low density lipoprotein receptor 1 (LOX1), cholesterol 25-hydroxylase (CH25H), 25- hydroxycholesterol 7α-hydroxylase (CYP7B1) as well as retinoic acid-related orphan receptor alpha (RORα), a binding receptor for cholesterol metabolites. We further demonstrated that enhancement of CH25H/CYP7B1/RORα axis resulted from FS exposure was mediated by activation of NF-κB signaling, along with upregulation in catabolic factors including matrix metallopeptidases (MMP3 and MMP13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2) in chondrocytes. Exogenous cholesterol acts synergistically with FS in activating NF-κB pathway and increases cholesterol metabolism. While, the addition of tauroursodeoxycholic acid (TUDCA) which promotes cholesterol efflux, resulted in remarkable reduction of intracellular cholesterol level and restoration of balance between anabolism and catabolism in FS treated chondrocytes. Collectively, our data indicated that, in response to FS of S. aureus, NF-κB signaling activation coupled with increased cholesterol metabolism to stimulate catabolic factors in chondrocytes, highlighting cholesterol metabolism as a potential therapeutic target for treating septic arthritis.

PAPA-like syndrome with heterozygous mutation in the MEFV gene.

A patient presented with a history of recurrent pyoderma gangrenosum, arthritis and extensive acne, prompting a genetic workup for PAPA syndrome. An MEFV mutation was identified and a change in therapeutic strategy from anakinra to colchicine was successful. Click https://www.wileyhealthlearning.com/#/online-courses/b52447c0-1d37-472d-b0c0-7817352d6f68 for the corresponding questions to this CME article.

Microbiological diagnosis of polymicrobial periprosthetic joint infection revealed superiority of investigated tissue samples compared to sonicate fluid generated from the implant surface.

OBJECTIVES: In the microbiological diagnosis of periprosthetic joint infection (PJI), there is much discussion about the methodology of obtaining proper specimens, the processing technique, and suitable culture media. This retrospective study was conducted to analyse the accuracy of our culture techniques. METHODS: Tissue samples and components from 258 patients after revision arthroplasty of the hip, knee, and shoulder were investigated, and the results of tissue cultures (TC) were compared to those of sonicate fluid cultures (SFC). Furthermore, an evaluation was performed of the influence of different culture media on the detection rate. RESULTS: PJI was confirmed in 186 patients. The overall sensitivity of TC was no different to that of SFC (91.3% vs 90.8%, P = 1). In 153 cases (82.3%), TC and SFC showed concordant positive results. Results were discordant in 33 cases (17.7%). When differentiated according to the type of infection, TC showed significantly better results than SFC in detecting polymicrobial infections (97.0% vs 67.0%, P = 0.004). There were also significant differences between the culture media regarding the yield of microorganisms. CONCLUSIONS: TC was more effective in detecting co-infections. The best results were obtained using both TC and SFC. The choice of culture media has a significant influence on the quality of results.

Restoration of the hip geometry after two-stage exchange with intermediate resection arthroplasty for periprosthetic joint infection.

Two-stage exchange with intermediate resection arthroplasty (RA) is a well-established surgical procedure in the treatment of chronic periprosthetic joint infection (PJI), whereby a higher failure rate of final hip geometry restoration due to tissue contraction is controversially discussed. The aim was to evaluate radiographic changes of hip geometry parameters during PJI treatment and to determine the impact of the intermediate RA on the final joint restoration after reimplantation of a total hip arthroplasty (reTHA). Radiographic parameters (leg length (LL), femoral offset (FO), horizontal/vertical acetabular center of rotation distance (h/vCORD)) of 47 patients (mean age: 64.1 years) were measured on standard radiographs of the pelvis and compared between four different stages during PJI treatment (pre-replacement status (preTHA), primary total hip arthroplasty (pTHA), RA and reTHA). The RA duration (mean: 10.9 months) and the number of reoperations during this period (mean: n = 2.0) as well as their impact on hip geometry restoration were evaluated. Between preTHA and pTHA/reTHA an equivalent restoration was measured regarding the FO (p < 0.001/p < 0.001) and hCORD (p = 0.016/p < 0.001), but not regarding the LL and vCORD. In contrast, analysis revealed no influence of RA and an equivalent reconstruction of LL (p = 0.003), FO (p < 0.001), v/hCORD (p = 0.039/p = 0.035) at reTHA compared to pTHA. Furthermore, RA duration (p = 0.053) and the number of reoperations after RA (p = 0.134) had no impact on radiographic hip geometry restoration. The two-stage exchange with intermediate RA does not alter the preexisting hip joint parameters, whereby a good restoration of the final hip geometry, independent of the duration or the number of reoperations, can be achieved.

Altered keratinization and vitamin D metabolism may be key pathogenetic pathways in syndromic hidradenitis suppurativa: a novel whole exome sequencing approach.

BACKGROUND: Diagnosis of pyoderma gangrenosum, acne and hidradenitis suppurativa (PASH) and pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) patients, in spite of recently identified genetic variations, is just clinical, since most patients do not share the same mutations, and the mutations themselves are not informative of the biological pathways commonly disrupted in these patients. OBJECTIVE: To reveal genetic changes more closely related to PASH and PAPASH etiopathogenesis, identifying novel common pathways involved in these diseases. METHODS: Cohort study on PASH (n = 4) and PAPASH (n = 1) patients conducted using whole exome sequencing (WES) approach and a novel bioinformatic pipeline aimed at discovering potentially candidate genes selected from density mutations and involved in pathways relevant to the disease. RESULTS: WES results showed that patients presented 90 genes carrying mutations with deleterious and/or damage impact: 12 genes were in common among the 5 patients and bared 237 ns ExonVar (54 and 183 in homozygosis and heterozygosis, respectively). In the pathway enrichment analysis, only 10 genes were included, allowing us to retrieve 4 pathways shared by all patients: (1) Vitamin D metabolism, (2) keratinization, (3) formation of the cornified envelope and (4) steroid metabolism. Interestingly, all patients had vitamin D levels lower than normal, with a mean value of 10 ng/mL. CONCLUSION: Our findings, through a novel strategy for analysing the genetic background of syndromic HS patients, suggested that vitamin D metabolism dysfunctions seem to be crucial in PASH and PAPASH pathogenesis. Based on low vitamin D serum levels, its supplementation is envisaged.

Role of different Th17 and Treg downstream signalling pathways in the pathogenesis of Staphylococcus aureus infection induced septic arthritis in mice.

Septic arthritis is a condition of bone disorder caused predominantly by Staphylococcus aureus. Following the bacterial entry activated immune cells specially macrophages and dendritic cells release pro-inflammatory mediators such as IL-6, TNF-α, IL-1ß etc., which not only create an inflammatory microenvironment but also play crucial roles in the proliferation of different CD+ T cell subsets. Among them, Th17 and Tregs are of major concern in recent times because of their potential roles in regulating the ongoing inflammation in many diseases including experimental arthritis. But the downstream signalling mechanism of these cells in regulating the severity of inflammation in case of septic arthritis is not known yet. So, here we have established a murine model of S. aureus induced septic arthritis and kept the animal upto 15 days post-infection. To examine the signalling mechanism, Th17 and Treg cells were isolated from blood, spleen and synovial joints of control and infected mice and observed the expression of JNK, NFκB and RANKL in the lysate of isolated Th17 and Tregs. We have also estimated the levels of serum IL-21 and TGF-ß. NFκB, JNK and RANKL expression was found to be higher at 3 and 15 days post-infection along with serum IL-21 levels. On the other hand, maximum TGF-ß level was observed at 9 days post-infection along with increased Treg population. In conclusion it was hypothesized that bone resorption is related with downstream signalling pathways of Th17 cells, which stimulate osteoclast generation via NFκB/JNK-RANKL axis and helps in the persistence of the disease.

The role of Staphylococcus aureus lipoproteins in hematogenous septic arthritis.

Permanent joint dysfunction is a devastating complication in patients with septic arthritis. Staphylococcus aureus (S. aureus) lipoproteins (Lpp), the predominant ligands for TLR2, are known to be arthritogenic and induce bone destruction when introduced directly into the joint. Here, we aim to investigate the importance of S. aureus Lpp and TLR2 in a hematogenous septic arthritis model, which is the most common route of infection in humans. C57BL/6 wild-type and TLR2 deficient mice were intravenously inoculated with S. aureus Newman parental strain or its lipoprotein-deficient Δlgt mutant strain. The clinical course of septic arthritis, radiological changes, and serum levels of cytokines and chemokines, were assessed. Newman strain induced more severe and frequent clinical septic polyarthritis compared to its Δlgt mutant in TLR2 deficient mice, but not in wild-type controls. Bone destruction, however, did not differ between groups. Lpp expression was associated with higher mortality, weight loss as well as impaired bacterial clearance in mouse kidneys independent of TLR2. Furthermore, Lpp expression induced increased systemic pro-inflammatory cytokine and neutrophil chemokine release. Staphylococcal Lpp are potent virulence factors in S. aureus systemic infection independent of host TLR2 signalling. However, they have a limited impact on bone erosion in hematogenous staphylococcal septic arthritis.

[Detection of Actinobacillus equuli ssp. equuli in piglets with purulent polyarthritis and tendovaginitis]. / Nachweis von Actinobacillus equuli ssp. equuli bei Saugferkeln mit eitriger Polyarthritis und Tendovaginitis.

Actinobacillus equuli ssp. equuli is an opportunistic pathogen in horses, mainly known to cause "sleepy foal disease". In comparison to horses, there are only few reports describing diseases in pigs associated with this gram-negative bacterium. This case report describes an outbreak of infection in a combined farrow-to-finish-farm. In September 2018, the following symptoms were noticed in one third of all newborn piglets from gilts and sows: 6-8 hours after birth piglets became weak and developed swollen joints with moderate to severe lameness. The piglets exhibited lethargy, a subset were non-ambulatory. An elevated piglet mortality within the first days within birth was noted. Seven piglets that succumbed to the disease (days 2-3 of life) were submitted for examination, 4 of which underwent pathological examination. The main findings were purulent polyarthritis and tendovaginitis. In addition, purulent inflammation was detected in the brain and kidneys of one animal. In the bacteriological examination A. equuli ssp. equuli was isolated in a total of 18 samples (brain, joints, suppurative structures of limbs), in a subset of cases as pure culture. For identification, cultural and biochemical characteristics were tested and a mass spectrometry analysis (MALDI-TOF MS) was performed. Further laboratory testing included 16 S rRNA-gene sequencing, a PCR in order to examine for special apx toxin genes as well as a PCR differentiating the two subspecies of A. equuli. It was not possible to identify the source of infection and routes of spread within the pig herd. The bacterial isolates were used for the production of an autogenous vaccine.

Etoposide-mediated depletion of peripheral blood monocytes post s.aureus infection attenuates septic arthritis by modulating macrophage-derived factors responsible for inflammatory destruction.

S.aureus induced septic arthritis remains a serious medical concern due to its rapidly progressive disease profile. The multidrug resistant nature of S.aureus demands the development of new strategies for the treatment of S.aureus arthritis. Since monocyte/macrophage population has been recognized as an important axis in joint inflammation and destruction, selective depletion of peripheral blood monocytes might influence the outcome and progression of the disease. Therefore, in this study we have put forward the concept of monocyte depletion by using etoposide, a drug that selectively depletes the monocyte/macrophage population. Mice were inoculated with live S.aureus for the development of septic arthritis. Post S.aureus infection, etoposide was subcutaneously injected. The severity of arthritis was found to be significantly low in the etoposide treated mice throughout the course. Arthritis index, histopathological analysis and TRAP staining images confirmed effectiveness of etoposide treatment in regulating inflammation and bone cartilage destruction. Lower levels of inflammatory cytokines, ROS, MMP-2, RANKL, OPN and plasmin reflected less severe arthritic destruction after etoposide treatment in arthritic mice. The bacterial load was not increased after etoposide treatment. Together, the presented data suggested that monocyte depletion by etoposide might represent an alternative therapeutic strategy for the treatment of S.aureus arthritis.

Multicentric Septic Osteomyelitis and Arthritis Caused by Staphylococcus aureus in a Gyrfalcon (Falco rusticolus).

An adult female gyrfalcon (Falco rusticolus) was presented with a right-wing droop and weight loss. Radiographic images revealed osteolysis and osseous proliferation of the right shoulder and the mobile vertebra between the notarium and synsacrum. The tentative diagnosis was vertebral osteomyelitis secondary to septic arthritis. The bird did not respond to antibiotic and anti-inflammatory therapy and represented 10 days later, with feathers soiled with feces, an impacted, dilated cloaca, and an inability to stand due to spastic paralysis of the hind legs. The bird's condition did not improve with 24 hours of supportive care and its quality of life was considered poor; therefore, the patient was euthanatized and submitted for postmortem examination. Multicentric septic osteomyelitis and arthritis were confirmed in the mobile vertebra between the notarium and synsacrum and the right shoulder. Despite 10 days of antibiotic therapy, Staphylococcus aureus was isolated from within the 2 locations in which septic osteomyelitis and arthritis were identified. This report describes the clinical features, diagnosis, and pathologic findings of septic osteomyelitis and arthritis caused by S aureus in a falcon.

Septic arthritis of the wrist: about six cases.

The wrist is a rare location of septic arthritis. It often involves patients with preexisting joint disease which symptoms could be confused with infection making the diagnosis more difficult and usually delayed. It is often responsible for residual functional impairment and for a high mortality rate among vulnerable patients. We report 6 cases of septic arthritis of the wrist in 3 males and 3 females. The mean age was 32 years in the male patients and 66 in the female patients. All the women were followed for rheumatoid arthritis. Biological results showed elevated rates of white blood cells and c-reactive protein in all the patients. Joint fluid analyses showed elevated white blood cell count. The treatment was medico-surgical consisting in synovectomy, joint debridement and immobilization of the wrist. At the average follow-up of 1 year and 4 months, 3 patients recovered a perfect mobility of the wrist without any limitation of the range of motion nor the strength. Three patients developed stiffness of the wrist.

A novel mouse model for septic arthritis induced by Pseudomonas aeruginosa.

Septic arthritis is one of the most aggressive joint diseases. Although caused predominantly by S. aureus, Gram-negative bacteria, Pseudomonas aeruginosa among them, account for a significant percentage of the causal agents of septic arthritis. However, septic arthritis caused by P. aeruginosa has not been studied thus far, due to lack of an animal model. NMRI mice were inoculated with different doses of P. aeruginosa. The clinical course of septic arthritis and radiological changes of joints were examined. Furthermore, the host molecular and cellular mechanisms involved in P. aeruginosa-induced septic arthritis were investigated. Inoculation of mice with P. aeruginosa caused septic arthritis in a dose-dependent manner. Neutrophil depletion led to higher mortality and more severe joint destruction (p < 0.01). In contrast, monocyte depletion resulted in higher mortality (p < 0.05) but similar arthritis severity compared to controls. Mice depleted of CD4+ T-cells inoculated with P. aeruginosa displayed less severe bone damage (p < 0.05). For the first time, a mouse model for P. aeruginosa septic arthritis is presented. Our data demonstrate that neutrophils play a protective role in P. aeruginosa septic arthritis. Monocytes/macrophages, on the other hand, are only essential in preventing P. aeruginosa-induced mortality. Finally, CD4+ T-cells are pathogenic in P. aeruginosa septic arthritis.

Development of a multiplex and sensitive lateral flow immunoassay for the diagnosis of periprosthetic joint infection.

The diagnosis of periprosthetic joint infection (PJI) remains a challenge. However, recent studies showed that synovial fluid biomarkers have demonstrated greater diagnostic accuracy than the currently used PJI diagnostic tests. In many diagnostic tests, combining several biomarkers into panels is critical for improving diagnostic efficiency, enhancing the diagnostic precision for specific diseases, and reducing cost. In this study, we prove that combining alpha-defensin and C-reactive protein (CRP) as biomarkers possesses the potential to provide accurate PJI diagnosis. To further verify the result, we developed a multi-target lateral flow immunoassay strip (msLFIA) with staking pad design to obtain on-site rapid response for clinical diagnosis of PJI. A total of 10 synovial fluid samples were tested using the msLFIA, and the results showed that the combined measurements of synovial fluid alpha-defensin and CRP levels were consistent with those obtained from a commercial enzyme-linked immunosorbent assay kit. In addition, we developed a multi-target lateral flow immunoassay strip (msLFIA) with staking pad design to obtain on-site rapid response for clinical diagnosis of PJI, which the multi-target design is used to increase specificity and the stacking pad design is to enhance detection sensitivity. As a result, the turnaround time of the highly sensitive test can be limited from several hours to 20 min. We expect that the developed msLFIA possesses the potential for routine monitoring of PJI as a convenient, low-cost, rapid and easy to use detection device for PJI.

Lack of Additional Diagnostic Yield of 16s rRNA Gene PCR for Prosthetic Joint Infections.

INTRODUCTION: Medical management of prosthetic joint infections (PJIs) relies on the identification of causative organisms through traditional culture-based approaches to guide therapy. However, diagnosis of many PJIs remains challenging, with many clinically apparent infections remaining culture-negative. Molecular diagnostics have the potential to increase diagnostic yield, particularly among culture-negative PJIs. METHODS: Bone, tissue, or synovial fluid from patients with clinically identified PJIs were collected for inclusion in this study. Samples were assessed with traditional cultures and classified as culture-positive or -negative after 48 h. Samples subsequently underwent a Staphylococcus aureus-/Kingella kingae-specific PCR followed by a 16s rRNA gene PCR. RESULTS: A total of 77 unique patients with clinically identified PJIs contributed a total of 89 samples for inclusion in the study. There were 54 culture-negative and 35 culture-positive samples evaluated. The sensitivity and specificity of S. aureus PCR in culture-positive samples was 57.1% (95% CI, 34.1%-78.1%) and 92.9% (95% CI, 66.1%-98.9%), respectively. Among culture-positive samples, 16s rRNA gene PCR correctly identified 3 of 21 (14.3%) samples with S. aureus and 2 of 5 (40%) samples with Streptococcus spp. All molecular tests were negative in those with clinically identified, culture-negative PJI. CONCLUSIONS: Our study suggests that these diagnostic tools have a limited role in PJI diagnosis.