Crystal-related Arthropathies Research Articles

Mechanism of Biqi capsules in the treatment of gout based on network pharmacology and experimental verification

Ethnopharmacological relevanceGout is a crystal-related arthropathy caused by monosodium urate (MSU) deposition, resulting from purine metabolism disorders and hyperuricemia (HUA). Gout belongs to the traditional medicine category of Bi syndrome. Biqi capsules (BQ) is a traditional Chinese medicine formula used to treat Bi syndrome. The BQ prescription is derived from the ancient prescription of Hua Tuo, a famous physician in the Han Dynasty. Aim of the studyTo study the effect and mechanism of BQ in treating acute gouty arthritis (AGA) and HUA. Materials and methodsAnalyzing BQ's signaling pathways for gout treatment via network pharmacology. The HUA model was induced orally with adenine and potassium oxonate. The rat AGA model was established by MSU injection. In vitro, MH7A and RAW 246.7 cells were treated with LPS and MSU. Serum uric acid, creatinine, and urea nitrogen levels were evaluated. Kidney and ankle joint pathology was observed via HE staining. Inflammatory signaling pathway proteins, epithelial-mesenchymal transition (EMT) pathway proteins, and uric acid metabolism-related proteins were detected by Western blot. Results1780 potential targets for gout treatment were identified, and 1039 target proteins corresponding to BQ's active ingredients were obtained. Pathway enrichment analysis revealed BQ improved gout mainly through inflammatory pathways. Experimental results showed BQ could reduce serum uric acid level and increase uric acid clearance rate by regulating the expression of adenosine deaminase (ADA), and organic anion transporter 1 (OAT1) and glucose transporter 9 (GLUT9) in HUA mice. BQ could improve renal function and injury by inhibiting the NLRP3 pathway in HUA mice' kidneys. Additionally, BQ could alleviate ankle joint swelling and synovial injury, inhibit the TLR4/NLRP3 pathway, and reduce levels of inflammatory factors including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) in AGA rats. The main component of BQ, brucine, could inhibit the activation of NLRP3/NF-κB pathway induced by MSU and reduce the expression level of inflammatory factors (IL-6, IL-1β, and TNF-α) in macrophages. Brucine could inhibit the activation of the EMT pathway and reduce the expression level of inflammatory factors (IL-6, TNF-α) in human fibroblast-like synoviocytes (MH7A cells) induced by MSU. ConclusionsBQ effectively reduced serum uric acid levels, improved kidney and joint damage, and ameliorated the inflammatory response caused by MSU. Its main component, brucine, effectively improved the inflammatory response and reduced the invasive ability of synoviocytes induced by MSU.

Facet joint involvement in the inflammatory rheumatic disease

BackgroundThe involvement of facet joints (FJ) in patients with inflammatory rheumatic disorders remains underexplored. This review aims to look at FJ disease from a rheumatologist's perspective, with the emphasis given to the clinical presentations and patterns of FJ engagement in axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and crystal-related arthropathies, and discussion of challenges in studying FJ in rheumatic disease. MethodsA systematic PubMed search using the pertinent keywords was performed, relevant articles extracted, and the acquired data critically assessed, interpreted, and organized according to the authors’ experience and judgment. ResultsFJ involvement is common in patients with radiographic axSpA, occurs throughout the spine, but is more frequently seen in the thoracic segment. The existing data suggests that the FJ are primarily affected by the disease process, while altered spine biomechanics due to the presence of syndesmophytes at the same vertebral level contributes to the FJ fusion. Predominant involvement of FJ of the cervical spinal segment has been suggested in PsA; however, prevalence and clinical significance of FJ involvement in PsA is still markedly underexplored. RA-related FJ disease of the cervical spine in patients with poorly controlled RA is not uncommon and can be related to significant morbidity, while the burden of FJ involvement in the thoracic and lumbar spinal segments in RA is also underexplored. FJ disease is possible in the course of crystal-related arthropathies, but the high level of suspicion is a prerequisite for the timely diagnosis. ConclusionsThe involvement of FJ in the course of inflammatory rheumatic disease is not uncommon. Prospective studies are needed to understand the epidemiology and significance of FJ disease in inflammatory rheumatic conditions.

Diagnosis and Treatment of Calcium Pyrophosphate Deposition (CPPD) Disease: A Review.

Calcium Pyrophosphate Dihydrate (CPPD) crystal-related arthropathies are a common cause of acute and chronic arthritis caused by the deposition of calcium pyrophosphate crystals in joints and soft tissues, resulting in inflammation and joint damage. They present with a wide spectrum of clinical manifestations and often present challenges to diagnosis and management as they commonly affect older co-morbid patients. The challenges are compounded by a lack of a well-defined description of CPPD. However, an international expert-driven process is underway to develop CPPD classification criteria. Treatment is also problematic as unlike gout, there are no agents available that decrease the crystal burden. Treatment options have often been extrapolated from gout treatment pathways without having extensive trials or a solid evidence base. It is hoped the new CPPD classification guidelines will contribute to large multicentre studies, with well-defined patient cohorts, which will facilitate the production of high-quality evidence to guide the management of this condition. Here, we discuss the barriers and facilitators in diagnosing and treating CPPD-related arthropathy.

Heritability of crystal related arthropathies

The most common types of crystal arthropathies are gout and calcium pyrophosphate deposition (CPPD) disease. Serum urate levels are influenced by a combination of genetic factors and the environment. There are studies estimating the heritability of urate ranging from 45% to 73%. Approximately 3% of the variance in serum urate level is explained by the locus SLC2A9. Among the Caucasian population, 10% of all gout cases may be largely attributable to locus ABCG2. Loss or reduction function of ABCG2 halves the kidney’s ability to secrete uric acid. Gain-of-function mutations in ENPP1 gene may be involved in the development of CPPD disease. Loss-of-function mutations in ANKH leads to excess calcium hydroxyapatite formation. Conclusions: There is reason to believe that studying susceptibility genes for the crystal arthropathies will contribute to our understanding of the complexity of inheritance of these disorders. At present many other genes involved in crystal arthropathies are being investigated, and we hope that soon, novel therapeutic targets will be found.

Dual-energy computed tomography in crystalline arthritis: knowns and unknowns.

To give an overview of what can reasonably be considered as known about dual-energy computed tomography (DECT) in crystal-related arthropathies, and what still needs to be explored. Recent studies suggest an overall superiority of DECT over ultrasound in gout in terms of sensitivity (89 vs. 84%) and specificity (91 vs. 84%), except in early disease. Additional studies are needed to optimize DECT postprocessing settings in order to improve the specificity of the technique and eliminate all artifacts. Evidence has been controversial concerning DECT's ability to detect monosodium urate (MSU) crystal deposits on vessel walls, or whether or not MSU-coded plaques are artifacts. DECT can be used to monitor MSU crystal depletion during urate-lowering treatment; MSU crystal volume is associated with cardiovascular risk and disease activity. There are some reports on calcium-containing crystal deposition diseases (calcium pyrophosphate and basic calcium phosphate) demonstrating that DECT can characterize and discriminate between the different types of crystals. Our knowledge about the use of DECT in crystal-related arthropathies continues to expand. Some unknowns have been clarified but there's still lots to learn, particularly concerning gout management and the potential use of DECT in calcium-containing crystal-related arthropathies.

O14 An atypical femoral fracture without a history of bisphosphonate use

Case report - IntroductionA 60-year-old female presented with an insufficiency fracture of the midshaft of the left femur and a persistently low serum alkaline phosphatase. A diagnosis of adult hypophosphatasia was made. We present this case alongside a series of other cases that we have identified locally and discuss the importance of identifying this condition in clinical practice.Case report - Case descriptionA 60-year-old female presented with left thigh pain and an 8-year history of polyarthralgia involving the medium-large sized joints. She had a traumatic fracture of the humerus 4 years previously. She had no history or examination findings suggestive of an inflammatory arthritis, connective tissue disease or systemic illness.An X-ray of left femur revealed a cortical-based lucency at the lateral cortex of midshaft. An MRI identified a focal area of cortical thickening but no evidence of bone marrow oedema suggestive of an osteoid osteoma. Finally, a CT scan confirmed the diagnosis of a healed stress fracture. The patient had never received any form of bisphosphonate treatment, no previous history of a non-traumatic fracture and no history of dental problems.Laboratory evaluation revealed persistently low levels of serum alkaline phosphatase (∼23 IU/L) with a normal vitamin D and PTH level. Bone density scan showed a T-score of -1.1 at the femoral neck and -2.6 at the lumbar spine. Serum pyridoxal phosphate level was elevated at 457 nmol/L (35-100). A diagnosis of adult hypophosphatasia was suspected and genetic study for ALPL gene confirmed the diagnosis.The following table summarises a number of other cases of adult hypophosphatasia, which we have identified locally. CaseAge / GenderPresentationAlkaline phospha tase (IU/L)Pyridoxal phosphate (nmol/L)Notes1 (Index case)62 / FWidespread pain, Atypical femoral fracture23457Genetic study confirmed278 / FWidespread pain, Osteomalacia22201Genetic study confirmed356 / MSon of Case 2, Osteoporosis, Diabetes mellitus22 – 29awaited Bisphosphonate stoppedGenetic study awaited 440 / FRecurrent metatarsal fractures, Low BMD24NormalBisphosphonate stopped548 / FPremature loss of teeth, fatigue, Widespread pain, Diabetes mellitus, hyperlipidaemia13-23327Genetic study confirmed675 / FSeronegative polyarthritis21-26120Genetic study awaitedCase report - DiscussionHypophosphatasia (HPP) is a rare inherited metabolic disease caused by mutations in the alkaline phosphatase liver type (ALPL) gene, localized on the chromosome region 1p36.1–34, encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). The disease is related to a decrease in both level and activity of alkaline phosphatase enzyme (ALP). The clinical expression is highly variable, ranging from lethal forms to mild forms diagnosed in adults. Fractures, chondrocalcinosis, calcific periarthritis, and chronic muscle and bone pain are key features for the diagnosis of HPP in adults. Teriparatide has been used for treatment in some case reports with inconsistent results. Antiresorptive drugs are contraindicated as they can worsen underlying osteomalacia.Case report - Key learning pointsCheck for persistent low serum alkaline phosphatase levels in adults presenting with fragility fractures, crystal-related arthropathies and nonspecific generalised aches.Avoid bisphosphonates in patients with low alkaline phosphatase.

Imaging of crystalline arthropathy in 2020.

Crystal-related arthropathies are the result of crystal deposition in joint and periarticular soft tissues. Identification of urate crystals is mandatory to distinguish gout from other crystalline arthropathies, including calcium pyrophosphate dihydrate and basic calcium phosphate crystal deposition diseases. ACR/EULAR classification criteria for gout included dual-energy computed tomography and ultrasound with equal impact to the final score. Different diagnostic strengths of these imaging modalities depend on disease duration and scanned anatomic site. While ultrasound has been indicated as the first-choice imaging technique, especially in the early stages of the disease, dual-energy computed tomography has shown to be highly specific, allowing the detection of crystal deposits in anatomic sites not accessible by ultrasound, such as the spine. At the spinal level, MRI findings are usually nonspecific. Finally, there is preliminary evidence that at the knee, dual-energy computed tomography may discriminate calcium pyrophosphate dihydrate from basic calcium phosphate crystal deposits.

Study of synovial fluid for crystals by polarized microscopy for degenerative and metabolic joint diseases

Background: Synovial fluid cytology is indicated in many joint diseases. There light microscopy fails to detect the pathognomic crystals deposited within synovial fluid which is closely related to the pathogenesis of osteoarthritis (OS) and other crystal related arthropathies. The polarized microscopy, therefore, is indicated for the examination of such fluids. Objectives: The comparison was drawn between light microscopy synovial fluid examination and polarized microscopy in the detection of pathognomic crystals. Materials and Methods: Thirty synovial fluids with varied clinicoradiological diagnosis aspirated from mostly large joints underwent conventional cytology by light microscopy and polarized microscopy. The rate of detection of crystals was evaluated. Results: The thirty patients in an age range of 21–80 years were recruited for the study. The crystals of calcium oxalate, monosodium urate, Charcot–Leyden crystals, cholesterol, homocysteine, and calcium pyrophosphate were assessed for deposition. It showed that light microscopy examination detected in six samples, whereas polarized microscopy detected in 14 samples. The rate of detection of crystals by polarized microscopy is more than twice that of light microscopy. The PPV and NPV for polarized microscopy are 100. Conclusion: Polarized microscopy of synovial fluid is advised to be carried out in the detection of crystal deposition in arthropathies for the earliest and appropriate management of the patient.

Osteoarthritis-associated basic calcium phosphate crystals alter immune cell metabolism and promote M1 macrophage polarization

A number of studies have demonstrated that molecules called 'alarmins' or danger-associated molecular patterns (DAMPs), contribute to inflammatory processes in the OA joint. Metabolic reprogramming of immune cells, including macrophages, is emerging as a prominent player in determining immune cell phenotype and function. The aim of this study was to investigate if basic calcium phosphate (BCP) crystals which are OA-associated DAMPs, impact on macrophage phenotype and metabolism. Human monocyte derived macrophages were treated with BCP crystals and expression of M1 (CXCL9, CXCL10) and M2 (MRC1, CCL13)-associated markers was assessed by real-time PCR while surface maturation marker (CD40, CD80 & CD86) expression was assessed by flow cytometry. BCP induced metabolic changes were assessed by Seahorse analysis and glycolytic marker expression (hexokinase 2(HK2), Glut1 and HIF1α) was examined using real-time PCR and immunoblotting. Treatment with BCP crystals upregulated mRNA levels of CXCL9 and CXCL10 while concomitantly downregulating expression of CCL13 and MRC1. Furthermore, BCP-treated macrophages enhanced surface expression of the maturation makers, CD40, CD80 and CD86. BCP-treated cells also exhibited a shift towards glycolysis as evidenced by an increased ECAR/OCR ratio and enhanced expression of the glycolytic markers, HK2, Glut1 and HIF1α. Finally, BCP-induced macrophage activation and alarmin expression was reduced in the presence of the glycolytic inhibitor, 2-DG. This study not only provides further insight into how OA-associated DAMPs impact on immune cell function, but also highlights metabolic reprogramming as a potential therapeutic target for calcium crystal-related arthropathies.

Dual-energy computed tomography in calcium pyrophosphate deposition: initial clinical experience

To determine the dual-energy computed tomography (DECT) attenuation properties of meniscal calcifications in calcium pyrophosphate deposition (CPPD) invivo, and assess whether DECT was able to discriminate meniscal CPP deposits from calcium hydroxyapatite (HA) in subchondral and trabecular bone. Patients with clinical suspicion of crystal-related arthropathy (gout and/or CPPD) and knee DECT scans were retrospectively assigned to CPPD (n=19) or control (n=21) groups depending on the presence/absence of chondrocalcinosis on DECT. Two observers drew standardized regions of interest (ROI) in meniscal calcifications, non-calcified menisci, as well as subchondral and trabecular bone. Five DECT parameters were obtained: CT numbers (HU) at 80 and 140kV, dual-energy index (DEI), electron density (ρe), and effective atomic number (Zeff). The four different knee structures were compared within/between patients and controls using linear mixed models, adjusting for confounders. Meniscal calcifications (n=89) in CPPD patients had mean±SD CT numbers at 80 and 140kV of 257±64 and 201±48 HU, respectively; with a DEI of 0.023±0.007, and ρe and Zeff of 140±35 and 8.8±0.3, respectively. Meniscal CPP deposits were readily distinguished from calcium HA in subchondral and trabecular bone (p≤0.001), except at 80kV separately (p=0.74). Zeff and ρe both significantly differed between CPP deposits and calcium HA in subchondral and trabecular bone (p<0.0001). This proof-of-concept study shows that DECT has the potential to discriminate meniscal CPP deposits from calcium HA in subchondral and trabecular bone invivo, paving the way for the non-invasive biochemical signature assessment of intra- and juxta-articular calcium crystal deposits.

Arthropathies microcristallines des sujets âgés

Crystal-related arthropathies are frequent in the elderly, among which the two most frequent are calcium pyrophosphate deposition disease (CPPD) and gout. These arthropathies classically induce acute arthritis whose diagnosis is made upon crystal identification by analysis of the synovial fluid with polarized-light microscopy. Without a crystal-proven confirmation, the diagnosis of these diseases can be a challenge and imaging techniques are increasingly helpful. Colchicine, non-steroidal anti-inflammatory drugs and glucocorticoids are commonly used to treat these arthropathies. Their use in the elderly is limited by frequent intolerance and contraindications so that interleukin-1 inhibitors are sometimes considered. Gout is the only crystal-related arthropathy with an existing treatment to deplete the pathogenic crystal, but therapeutic strategies exist to treat chronic PPCD, which can have polymorphous presentations.

Progress in Treatment of Gout Using Chinese and Western Medicine.

Gout is a crystal-related arthropathy resulting from the deposition of monosodium urate. Identifying appropriate treatments and novel drugs to decrease serum uric acid (SUA) levels and gout risk has been a major focus. By performing extensive literature review on the pathogenesis and Chinese and Western medicine treatment of gout, this paper aimed to identify novel targets for effective control of acute gout attacks and long-term reduction of SUA. In addition, we aimed to provide new directions for the improvement of therapeutic measures and the development of drugs. Although Western medicine can significantly contribute to the treatment of gout, Chinese herbal medicine has unique advantages, including reduced adverse reactions and higher patient compliance. It may also fill in the shortcomings of Western medicine in the intermittent period treatment of gout. In addition to constantly exploring pathogenesis and drug targets, research on Chinese herbal medicine is equally important. The combination of Chinese and Western medicine has proven to become an important direction for gout treatment.

50 Discrimination and characterization of calcium crystal types with a multi-energy spectral photon-counting CT for crystal-related arthropaties: Initial experience and diagnostic performance in vitro

Introduction Crystal-related arthropathies are a growing global health problem and imaging plays an important role in the diagnosis. Indeed, distinguishing crystal type, whether monosodium urate or one of the calcium crystal types is a clinical challenge because diagnosis and treatment depends on the crystal type involved. Although clinical imaging has made substantial progress in recent years, particularly with the development of dual-energy CT (DECT) protocols in people with longstanding and/or tophaceous gout, the diagnostic performance of DECT remains limited in the early stages of gout4. Moreover, while DECT is relatively accurate in distinguishing monosodium urate (MSU) from the various calcium deposits, there is currently no imaging technique capable of noninvasively differentiating one calcium crystal type from another in crystal-related arthropathies, whether in or around the joints. We aimed to determine the in vitro diagnostic performance of multi-energy spectral photon-counting CT (SPCCT) in crystal-related arthropathies. Methods Four crystal types (monosodium urate, MSU; calcium pyrophosphate, CPP; octacalcium phosphate, OCP; and calcium hydroxyapatite, CHA) were synthesized and blended with agar at the following concentrations: 240, 88, 46, and 72 mg/mL, respectively. Crystal suspensions were scanned on a pre-clinical SPCCT system at 80 kVp using the following four energy thresholds: 20, 30, 40, and 50 keV. Differences in linear attenuation coefficients between the various crystal suspensions were compared using the receiver operating characteristic (ROC) paradigm. Areas under the ROC curves (AUC), sensitivities, specificities, and diagnostic accuracies were calculated. Crystal differentiation was considered successful if AUC > 0.95. Results Multi-energy SPCCT can accurately differentiate MSU from CPP and CHA, CPP from OCP, and OCP from CHA in vitro. The distinction between MSU and OCP, and CPP and CHA is more challenging. Conclusions Multi-energy SPCCT can accurately differentiate MSU from CPP and CHA, CPP from OCP, and OCP from CHA in vitro. The distinction between MSU and OCP, and CPP and CHA is more challenging. The accurate identification and characterization of MSU and various calcium crystals would help improve both diagnosis and management of crystal-related arthropathies.

Imaging in Gout and Other Crystal-Related Arthropathies.

In this article, the authors consider the manifestations of intraarticular and periarticular crystal deposits. Most cases of crystal deposits are asymptomatic and represent incidental findings at imaging. In symptomatic arthropathies, imaging can play an important role in the diagnosis and assessment of disease progression and the extent of crystal deposits. Conventional radiography is the most common imaging modality. But ultrasound, conventional computerized tomography (CT), dual-energy CT, and MRI play an increasing role. The authors review typical radiographic features of crystal-induced arthropathies and findings that help to differentiate them. The authors also emphasize the increasing role of complementary imaging techniques.

General applications of ultrasound in rheumatology: why we need it in our daily practice.

Ultrasound (US) is a noninvasive imaging technique that continues to gain interest among rheumatologists because of its undoubted utility for the assessment of a wide range of abnormalities in rheumatic diseases. It also has a great potential to be used at the time of consultation as an extension of the clinical examination.Current data demonstrate that the standard clinical approach could result in an insensitive assessment of some the different aspects of the various rheumatic diseases for which US has become a feasible and effective imaging modality that allows early detection of anatomical changes, careful guidance for the aspiration and/or local treatment, and short- and long-term therapy monitoring at the joint, tendon, enthesis, nail, and skin levels. The spectrum of pathological conditions for which US plays a crucial role continues to increase over time and includes rheumatoid arthritis, spondyloarthropathies, osteoarthritis, crystal-related arthropathies, connective tissue disorders, and vasculitis.It is expected that the inclusion of more longitudinal studies with a larger number of patients and more rigorous methodological approach will undoubtedly provide a better understanding of the significance of the abnormal US findings detected in order to provide the proper diagnostic and/or therapeutic approaches. In this article, we analyze the current potential applications of US in rheumatology and discuss the evidence supporting its use in the daily rheumatologic practice.

Distinguishing gouty arthritis from calcium pyrophosphate disease and other arthritides.

Differentiating gout, calcium pyrophosphate deposition disease (CPPD), and non-crystal-related inflammatory arthropathies (non-CRA) is essential but often clinically impossible. The sonographic double contour (DC) sign may have good specificity for gout in highly specialized centers, but it can be challenging to use it to distinguish gout from cartilage hyperenhancements in CPPD. We evaluated the diagnostic value of the DC sign alone and in combination with Doppler signals and uric acid (UA) levels in patients with acute arthritis. We retrospectively investigated 225 acutely inflamed joints and documented the presence of DC, Doppler hypervascularization, and serum UA (SUA) levels. All patients underwent synovial fluid (SF) analysis. Sensitivity, specificity, and positive predictive values were calculated, and correlation analyses and a binary regression model were used to investigate their diagnostic values. The sensitivity of DC sign for crystalline arthritides was 85% and specificity 80%. Its specificity for gout was 64%, for CPPD 52%. In contrast to non-CRA hypervascularization, degree 2 and 3 Doppler signals were highly associated with gout and less with CPPD (p < 0.01). The combination of DC sign with hypervascularization and elevated UA levels increased specificity for gout to more than 90% and resulted in a 7-fold increase of the likelihood of diagnosis of gout (p < 0.01), but with a loss of sensitivity (42%). The DC sign alone is suitable for predicting crystal-related arthropathies, but it cannot reliably distinguish gout from CPPD in everyday clinical routine. Combining hypervascularization and SUA levels increases the diagnostic value, leading us to propose a diagnostic algorithm.

SP0026 Ultrasound Assessment of the Cartilage

Musculoskeletal ultrasound (US) is a valuable imaging modality for detecting and quantifying a range of joint pathologies occurring in rheumatic diseases (1-2). In inflammatory arthritis and in osteoarthritis (OA) it...

Epigallocatechin-3-gallate reduces inflammation induced by calcium pyrophosphate crystals in vitro

Although osteoarthritis (OA) is defined as a cartilage disease, synovitis involving mononuclear cell infiltration and overexpression of proinflammatory mediators is common in early and late OA. Calcium crystals deposition is thought to be a factor that likely contributes to synovial inflammation. In recent years, significant interest has emerged in the beneficial health effects attributed to the green tea polyphenols and in particular to epigallocatechin-3-gallate (EGCG). It has been demonstrated that some of the actions of EGCG are linked to its ability to interfere with cell membranes. The objective of this study was to evaluate the influence of EGCG in some inflammatory aspects of OA and whether EGCG is able to interfere with membrane organization. We assessed the effect of EGCG on the production of proinflammatory cytokines and chemokines released by human fibroblast-like synoviocytes (FLS) and THP-1 cells stimulated with calcium pyrophosphate (CPP) crystals in presence of methyl-β-cyclodextrin (MβCD), a cholesterol-removing agent that disturbs lipid raft structures. The chemotactic effect of culture supernatants was also evaluated. EGCG inhibited interleukin (IL)-1β, transforming growth factor beta, IL-8, and chemokine (C–C motif) ligand 2 (CCL2) release by stimulated FLS and/or THP-1 cells in a dose-dependent manner. Supernatants of CPP-stimulated cells induced the migration of neutrophils and mononuclear cells which decreased in a dose-dependent manner in the presence of EGCG. EGCG increased cell viability when added to THP-1 cells treated with MβCD. Furthermore, MβCD enhanced the inflammatory response to CPP crystals increasing IL-8 and CCL2 secretion which was inhibited by EGCG in a dose-dependent manner. This study showed that EGCG is able to reduce the inflammatory response induced by CPP crystals in vitro. The identification of EGCG as dietary supplement capable of affording protection or modulating the inflammatory response to CPP crystals may have important implications in the prevention and treatment of OA and crystal-related arthropathies.

Les arthropathies inflammatoires du coude

The inflammatory arthropathies of the elbow are mainly found in chronic inflammatory rheumatisms such as rheumatoid arthritis, spondylarthropthies, crystal-related arthropathies and hemophilia. The clinical examination of this superficial joint is easy. The tolerance is for a long time good except when the flexion is limited. The complementary explorations of imaging as the echography partner to the simple radiography are mostly enough.

Treatment and management of pseudogout: insights for the clinician

Pseudogout and the associated calcium pyrophosphate dihydrate (CPPD)- crystal-related arthropathies are common conditions that present particular management problems in clinical practice as they often affect older patients with multiple medical comorbidities. The epidemiology, metabolic and endocrine disease associations, and routine investigations used in the diagnostic workup are briefly reviewed. Current treatment approaches that are mainly directed at relieving the symptoms of joint inflammation are outlined. Unlike gout, there are no agents available that have been shown to decrease crystal load in CPPD-related joint disease. Recent novel insights into the pathogenesis of crystal-induced joint inflammation and subsequent joint degeneration are also discussed. The potential of colchicine as a prophylactic agent in managing recurrent attacks and the likely mechanisms of its effects on the NACHT, LRR and PYD domains-containing protein 3 (NALP-3) inflammasome of the innate immune system are highlighted. The use of agents that directly target the inflammasome, in particular drugs which inhibit the interleukin 1 pathway, in the treatment of severe, refractory pseudogout is also discussed. Finally, there is particular emphasis on the likely pathogenic role of CPPD crystal deposition in degenerative joint disease and the use of targeted anticrystal therapies as potential disease-modifying drugs.