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Calcium-containing crystal deposition diseases are a common cause of pain and disability but remain relatively under-investigated. No drug has been identified that can prevent deposition or effect dissolution of either calcium pyrophosphate (CPP) or basic calcium phosphate (BCP) crystals. In comparison to the field of gout and urate biology, published research in relation to calcium crystal deposition diseases in 2022 was relatively modest in quantity. In CPP deposition (CPPD) disease, progress was made mainly in epidemiology, imaging, surgical management and Gitelman's syndrome. In relation to BCP crystals, the effect on tenocytes in vitro was explored and results indicate that BCP crystals likely reduce tendon matrix integrity via their interaction with tenocytes. The involvement of calcification in the progression of osteoarthritis (OA) was elegantly demonstrated contributing to further discovery of the process of OA progression. There was a paucity of mechanistic and genetic studies in calcium crystal deposition diseases published in 2022, nor any breakthrough in therapy, showing that there is abundant scope for investigation under these themes in the future. [ABSTRACT FROM AUTHOR]

Sharon Cowley, Geraldine McCarthy Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, IrelandCorrespondence: Sharon Cowley, Mater Misericordiae University Hospital, Dublin, Ireland, Email sharoncowley111@gmail.comAbstract: 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.Keywords: crystal arthropathy, calcium pyrophosphate dihydrate, CPPD

Gout is caused by monosodium urate (MSU) crystal deposition within joints. This leads to acute episodes of inflammation ("gout flares") driven by NLRP3 inflammasome activation in macrophages. Gout flares are frequently present during late night/early morning. The reason for this timing is unclear. Recent evidence suggests the NLRP3 inflammasome is under circadian control. The purpose of this study was to determine whether MSU crystals cause changes in the circadian clock in macrophages leading to time‐of‐day differences in NLRP3 inflammasome activation. Levels of circadian clock components were measured in undifferentiated "monocytic" and PMA‐differentiated "macrophagic" THP‐1 cells cultured with/without MSU crystals. Caspase‐1 activity was measured to assess NLRP3 inflammasome activity. MSU crystal exposure resulted in minimal effects on clock genes in THP‐1 monocytes but BMAL1, CRY1, PER2, and REV‐ERBα showed altered expression with reduced protein levels of BMAL1 and REV‐ERBα in THP‐1 macrophages. REV‐ERBα activation or BMAL1 over‐expression resulted in reduced MSU crystal‐induced caspase‐1 activity. BMAL1 knockdown resulted in a further increase in MSU crystal‐induced caspase‐1 activity, but only at times of day when BMAL1 levels were naturally high. MSU crystal‐induced NLRP3 inflammasome activation was greatest at the time of day when BMAL1 levels were naturally low. MSU crystals alter the expression of circadian clock components in THP‐1 macrophages leading to loss of BMAL1 and REV‐ERBα‐mediated repression of NLRP3 inflammasome activity and time‐of‐day differences in susceptibility to inflammasome activation. Our findings suggest that the nocturnal risk of gout flare is at least partially a consequence of altered circadian control of immune cell function. [ABSTRACT FROM AUTHOR]

Abstract Background The coexistence of calcium pyrophosphate dihydrate crystal deposition (CPP) and synovial chondromatosis (SC) in the temporomandibular joint (TMJ) is rarely reported. CPP disease (CPPD) is complex arthritis synonymous with excessive pyrophosphate production and variable aberrations in mineral and organic phase metabolism of the joint cartilage, leading to local inundated CPP and crystal deposition of partially deciphered predispositions. Meanwhile, SC is a rare benign synovial joint proliferative disease of unclear etiology and has a low risk of malignant transformation. However, SC manifests severe joint disability and dysfunction because of connective tissue metaplasia of the synovial membrane, which forms cartilaginous nodules with or without calcifications or ossifications. These nodules often detach and form intra-articular loose bodies and very rarely within extraarticular spaces. Case presentation We report the case of a 61-year-old man to expand the body of literature on these unusual coexisting arthropathies of the TMJ. The patient presented to our hospital in 2020 with complaints of pain in the right TMJ and trismus for over 6 months. Radiographic assessments of the TMJ provided a preoperative provisional diagnosis of SC. However, the histopathology of the open biopsy revealed tumor-like lesions comprising several deposits of rhomboid and rod-shaped crystals that displayed positive birefringence in polarized light, confirming a coexistence of CPPD. A second-stage operation was performed for the complete removal of the loose bodies and chalk-like lesions including synovectomy. No evidence of recurrence was recorded after a follow-up of nearly 1.5 years. Conclusions Isolated CPPD and SC of the TMJ are prevalent in the literature however, monoarticular coexistence of these diseases is rare, due to the lack of consistency in the diagnostic criteria in clinical practice. Moreover, optimal treatment depends on several considerations. This report delineated the molecular etiopathology and underscored the need for continued deciphering of the causal mechanisms of coexisting CPPD and SC of the TMJ. In addition, the importance of confirmatory testing for accurate diagnosis, and appropriate management of these diseases were discussed.

Background: The coexistence of calcium pyrophosphate dihydrate crystal deposition (CPP) and synovial chondromatosis (SC) in the temporomandibular joint (TMJ) is rarely reported. CPP disease (CPPD) is complex arthritis synonymous with excessive pyrophosphate production and variable aberrations in mineral and organic phase metabolism of the joint cartilage, leading to local inundated CPP and crystal deposition of partially deciphered predispositions. Meanwhile, SC is a rare benign synovial joint proliferative disease of unclear etiology and has a low risk of malignant transformation. However, SC manifests severe joint disability and dysfunction because of connective tissue metaplasia of the synovial membrane, which forms cartilaginous nodules with or without calcifications or ossifications. These nodules often detach and form intra-articular loose bodies and very rarely within extraarticular spaces. Case presentation: We report the case of a 61-year-old man to expand the body of literature on these unusual coexisting arthropathies of the TMJ. The patient presented to our hospital in 2020 with complaints of pain in the right TMJ and trismus for over 6 months. Radiographic assessments of the TMJ provided a preoperative provisional diagnosis of SC. However, the histopathology of the open biopsy revealed tumor-like lesions comprising several deposits of rhomboid and rod-shaped crystals that displayed positive birefringence in polarized light, confirming a coexistence of CPPD. A second-stage operation was performed for the complete removal of the loose bodies and chalk-like lesions including synovectomy. No evidence of recurrence was recorded after a follow-up of nearly 1.5 years. Conclusions: Isolated CPPD and SC of the TMJ are prevalent in the literature however, monoarticular coexistence of these diseases is rare, due to the lack of consistency in the diagnostic criteria in clinical practice. Moreover, optimal treatment depends on several considerations. This report delineated the molecular etiopathology and underscored the need for continued deciphering of the causal mechanisms of coexisting CPPD and SC of the TMJ. In addition, the importance of confirmatory testing for accurate diagnosis, and appropriate management of these diseases were discussed. [ABSTRACT FROM AUTHOR]

To estimate the prevalence rate of gout and to explore the social factors that contributed to its development in the various sub-populations in medieval Cambridge. 177 adult individuals from four medieval cemeteries located in and around Cambridge, UK. Lesions were assessed macroscopically and radiographically. Elements with lytic lesions were described and imaged using micro-computed tomography (μCT) to determine their morphology. Gout was identified in 3 % of the population. Individuals buried in the friary had highest prevalence (14 %), with low prevalence rates in the Hospital (3 %) and town parish cemetery (2 %), with no cases in the rural parish cemetery. Gout was more prevalent during the 14th–15th centuries than the 10th–13th centuries. The high prevalence rate of gout in the friary is at least partly explained by the consumption of alcohol and purine-rich diets by the friars and the wealthy townsfolk. Medieval medical texts from Cambridge show that gout (known as podagra) was sometimes treated with medications made from the root of the autumn crocus. This root contains colchicine, which is a medicine that is still used to treat gout today. This is one of the first studies to assess the epidemiology of gout in medieval England and suggests that gout varied with social status. Our sample size precludes statistical analysis. Additional studies that assess the epidemiology of gout in medieval Europe is needed in order to be able to fully contextualize these findings. [ABSTRACT FROM AUTHOR]

Objective: To describe the characteristics of calcium pyrophosphate (CPP) crystal size and morphology under compensated polarized light microscopy (CPLM). Secondarily, to describe CPP crystals seen only with digital enhancement of CPLM images, confirmed with advanced imaging techniques. Methods: Clinical lab-identified CPP-positive synovial fluid samples were collected from 16 joint aspirates. Four raters used a standardized protocol to describe crystal shape, birefringence strength and color. A crystal expert confirmed CPLM-visualized crystal identification. For crystal measurement, a high-pass linear light filter was used to enhance resolution and line discrimination of digital images. This process identified additional enhanced crystals not seen by raters under CPLM. Single-shot computational polarized light microscopy (SCPLM) provided further confirmation of the enhanced crystals’ presence. Results: Of 932 suspected crystals identified by CPLM, 569 met our inclusion criteria, and 293 (51%) were confirmed as CPP crystals. Of 175 unique confirmed crystals, 118 (67%) were rods (median area 3.6 ​μm2 [range, 1.0–22.9 ​μm2]), and 57 (33%) were rhomboids (median area 4.8 ​μm2 [range, 0.9–16.7 ​μm2]). Crystals visualized only after digital image enhancement were smaller and less birefringent than CPLM-identified crystals. Conclusions: CPP crystals that are smaller and weakly birefringent are more difficult to identify. There is likely a population of smaller, less birefringent CPP crystals that routinely goes undetected by CPLM. Describing the characteristics of poorly visible crystals may be of use for future development of novel crystal identification methods.

Objective: To examine and compare the accuracy of conventional radiography (CR) and musculoskeletal ultrasonography (US) in the diagnosis of calcium pyrophosphate (CPP) crystals deposition disease (CPPD).Design: A systematic search of electronic databases (PubMed, Embase, and Cochrane), conference abstracts and reference lists was undertaken. Studies which evaluated the accuracy of CR and/or US in the diagnosis of CPPD, using synovial fluid analysis (SFA), histology or classification criteria as reference tests were included. Subgroup analyses by anatomic site and by reference test were performed.Results: Twenty-six studies were included. Using SFA/histology as reference test, CR and US showed an excellent (CR AUC = 0.889, 95%CI = 0.811-0.967) and an outstanding (US AUC = 0.954, 95%CI = 0.907-1.0) diagnostic accuracy (p < 0.01), respectively. Furthermore, US showed a higher sensitivity (0.85, 95%CI = 0.79-0.90 vs 0.47, 95%CI = 0.40-0.55) and only a little lower specificity (0.87, 95%CI = 0.83-0.91 vs 0.95, 95%CI = 0.92-0.97) than CR. A considerable heterogeneity between the studies was found, with adopted reference test being the main source of heterogeneity. In fact, subgroup analysis showed a significant change in the diagnostic accuracy of CR, but not of US, using Ryan and McCarty criteria or SFA/histology as reference test (CR: AUC = 0.956, 95%CI = 0.925-1.0 vs AUC = 0.889, 95%CI = 0.828-0.950, respectively, p < 0.01) (US: AUC = 0.922, 95%CI = 0.842-1.0 vs AUC = 0.957, 95%CI = 0.865-1.0, respectively, p = 0.08) CONCLUSIONS: Although US is more sensitive and a little less specific than CR for identifying CPP crystals, both these two techniques showed a great diagnostic accuracy and should be regarded as complementary to each other in the diagnostic work-up of patients with CPPD. [ABSTRACT FROM AUTHOR]

Objective: Little is known about acute calcium pyrophosphate (CPP) crystal arthritis flare rates and risk factors for recurrence. We characterized flares and determined the rate and predictors of acute CPP crystal arthritis flares in an academic medical center cohort.Methods: We performed a retrospective cohort study among a random sample of patients with acute CPP crystal arthritis identified in the Partners HealthCare electronic medical record, 1991-2017. Flare was defined as self-limited, acute-onset synovitis with synovial fluid CPP crystals and/or chondrocalcinosis, not better explained by another cause. We calculated incidence rates (IR) for acute CPP crystal arthritis flare among all subjects and by sex. We estimated HR for recurrent flare using univariate Cox models that accounted for within-person correlated data.Results: We identified 70 patients with acute CPP crystal arthritis with a total of 111 flares. Recurrent flares occurred in 24% of patients; half of flares occurred in a previously unaffected joint. The acute CPP crystal arthritis flare rate was 11.4 per 100 person-years overall (95% CI 8.2-15.4), 14.2 in women (95% CI 9.6-0.1), and 7.1 in men (95% CI 3.4-13.0). Cancer (HR 2.98, 95% CI 1.33-6.68) and chronic kidney disease (HR 2.92, 95% CI 1.10-7.76) were associated with a higher rate for recurrent flare.Conclusion: Recurrent flares occurred in about one-fourth of patients with acute CPP crystal arthritis and often occurred in previously unaffected joints. The acute CPP crystal arthritis flare rate was twice as high in women as in men. [ABSTRACT FROM AUTHOR]

Wenji Chen,1 Yanyan Wang,2 Yan Li,2 Zheng Zhao,2 Lixia Feng,2 Jian Zhu,2 Jianglin Zhang,2 Feng Huang2 1Department of Rheumatology, Hainan Branch of Chinese People’s Liberation Army General Hospital, Sanya, 2Department of Rheumatology, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China Abstract: Gout is clinically characterized by episodes of monoarthritis, which not only typically affects the peripheral joints but also occasionally affect the axial joint, such as the sacroiliac joint (SIJ), and often mimics spondyloarthritis (SpA). Two cases of gout mimicking SpA are presented in the current paper. One patient was a 32-year-old man with a history of asymmetrical oligoarthritis of ankle and metatarsophalangeal joints (MTPJ). He had left gluteal pain for 2 weeks. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the bone erosion of the left SIJ. T1-weighted MRI showed hypointense T1 and hyperintense T2 signals of the left SIJ. The other patient was a 24-year-old man with left back pain and hip pain for 4 months and intermittent fever for 3 months. He had a history of gout for 3 years. Both patients underwent CT-guided sacroiliac biopsy, and monosodium urate (MSU) crystals were shown by polarized microscopy. Gout can often mimic SpA and seldomly affects the SIJ. Thus, its correct diagnosis and adequate therapy can halt the development of such damaging complications. Keywords: gout, crystal arthropathy, sacroiliac joint, radiography

Objective To investigate temporal trends in the incidence and prevalence of gout in the adult Danish population. Methods Using the nationwide Danish National Patient Registry, we calculated the number of incident gout patients (per 100 000 person-years) within each 1 year period from 1995 to 2015 and the prevalence of gout in 2000 and 2015. Further, we calculated age- and gender-specific incidence rates of gout from 1995 to 2015. Results We identified a total of 45 685 incident gout patients (72.9% males) with a mean age of 65 years (s.d. 16) at diagnosis. In both genders, an increase in age-standardized incidence rates was observed from 32.3/100 000 (95% CI 30.7, 33.9) in 1995 to 57.5/100 000 (95% CI 55.6, 59.5) in 2015 (P < 0.001). Similar trends were observed for 8950 cases diagnosed in rheumatology departments. We likewise observed an increase in the prevalence of gout from 0.29% (95% CI 0.29, 0.30) in 2000 to 0.68% (95% CI 0.68, 0.69) in 2015. Conclusions The annual incidence rate of gout increased by almost 80% in Denmark between 1995 and 2015. The prevalence increased by nearly 130% between 2000 and 2015. Reasons for this are unknown but may include an increase in risk factors (e.g. obesity, diabetes mellitus), longer life expectancy and increased awareness of the disease among patients and/or health professionals. [ABSTRACT FROM AUTHOR]

In osteoarthritis, chondrocytes undergo a phenotype shift characterised by reduced expression of SOX9 (sry-box 9) and increased production of cartilage-degrading enzymes, e.g. MMP13 (matrix metalloproteinase 13) and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5). The chondrocyte clock is also altered. Specifically, the peak level of PER2 is elevated, but peak level of BMAL1 reduced in osteoarthritic chondrocytes. The purpose of this study was to determine whether increased PER2 expression causes disease-associated changes in chondrocyte activity and to identify whether known risk factors for osteoarthritis induce changes in PER2 and BMAL1 expression. Primary human chondrocytes isolated from macroscopically normal cartilage were serum-starved overnight then re-fed with serum-replete media with/without interleukin 1β (IL-1β) (10 ng/mL), hydrogen peroxide (100 µM) or basic calcium phosphate (BCP) crystals (50 µg/mL). Peak level of BMAL1 was lower, whereas PER2 levels remained elevated for longer, in chondrocytes treated with IL-1β, hydrogen peroxide or BCP crystals compared to untreated cells. Levels of SOX9 were lower, whereas levels of ADAMTS5 and MMP13 were higher, in chondrocytes exposed to any of the three treatments compared to untreated cells. Knockdown of PER2 using siRNA partially abrogated the effects of each treatment on chondrocyte phenotype marker expression. Similarly, in chondrocytes isolated from osteoarthritic cartilage PER2 knockdown was associated with increased SOX9, reduced ADAMTS5 and reduced RNA and protein levels of MMP13 indicating partial mitigation of the osteoarthritic phenotype. Conversely, further ablation of BMAL1 expression in osteoarthritic chondrocytes resulted in a further reduction in SOX9 and increase in MMP13 expression. Overexpression of PER2 in the H5 chondrocyte cell line led to increased ADAMTS5 and MMP13 and decreased SOX9 expression. Localised inflammation, oxidative stress and BCP crystal deposition in osteoarthritic joints may contribute to disease pathology by inducing changes in the chondrocyte circadian clock. [ABSTRACT FROM AUTHOR]

Chondrocytes in osteoarthritis undergo a phenotype shift leading to increased production of cartilage-degrading enzymes. There are similarities between the phenotype of osteoarthritic chondrocytes and those of growth plate chondrocytes. Hydroxyapatite can promote chondrocyte differentiation in the growth plate. Basic calcium phosphate (BCP) crystals (which consist of hydroxyapatite, octacalcium apatite and tricalcium phosphate) are frequently found in osteoarthritic joints. The objective of this study was to determine whether BCP crystals induce disease-associated changes in phenotypic marker expression in chondrocytes. Primary human chondrocytes isolated from macroscopically normal cartilage were treated with BCP for up to 48 h. Expression of indian hedgehog (IHH), matrix metalloproteinase 13 (MMP13), interleukin-6 (IL-6) and type X collagen (COLX) were higher, and expression of sry-box 9 (SOX9) lower, in BCP-treated chondrocytes (50 µg/mL) compared to untreated controls. COLX protein was also present in BCP-treated chondrocytes. Intracellular calcium and levels of phosphorylated and total calcium/calmodulin kinase 2 (CaMK2) were elevated following BCP treatment due to BCP-induced release of calcium from intracellular stores. CaMK2 inhibition or knockdown ameliorated the BCP-induced changes in SOX9, IHH, COLX, IL-6 and MMP13 expression. BCP crystals induce osteoarthritis-associated changes in phenotypic marker expression in chondrocytes by calcium-mediated activation of CaMK2. The presence of BCP crystals in osteoarthritic joints may contribute to disease progression. [ABSTRACT FROM AUTHOR]

In recent years significant advances have been made in imaging techniques. Dual-energy computed tomography has revolutionized the ability to detect and quantify gout. The key ultrasound features of gout have been defined. Magnetic resonance imaging is an excellent modality for demonstrating the extent and severity of crystal arthropathies, but the findings may be nonspecific. This article summarizes the use of advanced imaging techniques in the diagnosis and assessment of gout and other crystal arthropathies. [ABSTRACT FROM AUTHOR]

Gout is clinically characterized by episodes of monoarthritis, which not only typically affects the peripheral joints but also occasionally affect the axial joint, such as the sacroiliac joint (SIJ), and often mimics spondyloarthritis (SpA). Two cases of gout mimicking SpA are presented in the current paper. One patient was a 32-year-old man with a history of asymmetrical oligoarthritis of ankle and metatarsophalangeal joints (MTPJ). He had left gluteal pain for 2 weeks. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the bone erosion of the left SIJ. T1-weighted MRI showed hypointense T1 and hyperintense T2 signals of the left SIJ. The other patient was a 24-year-old man with left back pain and hip pain for 4 months and intermittent fever for 3 months. He had a history of gout for 3 years. Both patients underwent CT-guided sacroiliac biopsy, and monosodium urate (MSU) crystals were shown by polarized microscopy. Gout can often mimic SpA and seldomly affects the SIJ. Thus, its correct diagnosis and adequate therapy can halt the development of such damaging complications. [ABSTRACT FROM AUTHOR]

Résumé Introduction La chondrocalcinose est un rhumatisme microcristallin provoqué par la présence de cristaux de pyrophosphate de calcium dans l'articulation. Nous rapportons une observation exceptionnelle de pseudo-abcès musculaire microcristallin mimant une infection ostéo-musculaire de hanche. Observation Un homme de 92 ans était hospitalisé pour l'exploration de douleurs inguinales gauches subaiguës. À l'examen clinique, le patient présentait une douleur inguinale et un psoïtis. Le bilan biologique montrait un syndrome inflammatoire. L'imagerie mettait en évidence plusieurs collections au sein des muscles iliopsoas et petit glutéal associées à une arthrite de hanche gauche. La ponction des collections rapportait un liquide inflammatoire stérile. L'analyse anatomopathologique révélait des cristaux de pyrophosphate de calcium, confirmant le diagnostic de pseudo-abcès aseptique lié à une chondrocalcinose, probablement conséquence d'une bursite de hanche. Le traitement médical associé au drainage radioguidé était partiellement efficace, le patient récidivant sous la forme de bursites multiples. Conclusion L'atteinte de chondrocalcinose de hanche est rare, et son association à une atteinte musculaire est exceptionnelle, avec à notre connaissance seule 4 autres cas publiés dans la littérature. Le mécanisme le plus probable est une infiltration par contiguïté avec formation d'un pseudo-abcès aseptique musculaire. Un mécanisme primitif par néoformation musculaire de microcristaux est également discuté. Une revue des cas publiés dans la littérature montre une évolution favorable mais parfois au prix d'un drainage chirurgical. Cette atteinte doit être connue et distinguée des abcès musculaires d'origine infectieuse. Abstract Introduction Chondrocalcinosis results from calcium pyrophosphate crystals deposition in the joints. We report an exceptional case of aseptic psoas abscess with a deposition of calcium pyrophosphate crystals. Case report A 92-year-old man presented to our department for an acute onset of inflammatory pain in the left hip. Computed tomography detected a coxofemoral arthritis and multiple intramuscular collections located in the iliopsoas muscle and the gluteus minimus. A sample of the fluid was obtained with a guided aspiration, and its analysis revealed an inflammatory liquid with no bacteria but numerous calcium pyrophosphate crystals. The final diagnosis was thus a muscular calcium pyrophosphate deposition pseudo-abscess, associated with a hip arthritis. Conclusion Hip chondrocalcinosis is unusual, and the association with intramuscular deposition of calcium pyrophosphate crystals seems extremely rare as we found only four other published cases. A microcrystalline arthritis could have spread from the coxofemoral joint through the iliopsoas bursa and into the muscle. However, the imaging aspect with an abscess and a predominant muscular injury might suggest a mechanism of crystal formation originating directly within the muscle. The outcome was always favourable even if some patients required surgery. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the diagnostic value of single-source dual-energy computed tomography (SDECT) in gouty arthritis and to compare its capability to detect urate depositions with digital radiography (DR) and conventional computed tomography (CT).Methods: Forty-four patients who underwent SDECT volume scans of the feet for suspected gouty arthritis were retrospectively analyzed. SDECT, CT (both n=44) and DR (n=36) were scored by three blinded readers for presence of osteoarthritis, erosions, and tophi. A diagnosis was made for each imaging modality. Results were compared to the clinical diagnosis using the American College of Rheumatology (ACR) classification criteria.Results: The patient population was divided into a gout (n=21) and control (n=23) group based on final clinical diagnosis. Osteoarthritis was evident in 15 joints using CT and 30 joints using DR (p=0.165). There were 134 erosions detected by CT compared to 38 erosions detected by DR (p<0.001). In total 119 tophi were detected by SDECT, compared to 85 tophi by CT (p=0.182) and 25 tophi by DR (p<0.001). SDECT had best diagnostic value for diagnosis of gout compared to DR and conventional CT (sensitivity and specificity for SDECT: 71.4% and 95.7%, CT: 71.4% and 91.3% and DR: 44.4% and 83.3%, respectively). For all three readers, Cohen's kappa for DR and conventional CT were substantial for all scoring items and ranged from 0.75 to 0.77 and 0.72-0.76, respectively. For SDECT Cohen's kappa was good to almost perfect with 0.77-0.84.Conclusions: SDECT is capable to detect uric acid depositions with good sensitivity and high specificity in feet, therefore diagnostic confidence is improved. Using SDECT, inter-reader variance can be markedly reduced for the detection of gouty tophi. [ABSTRACT FROM AUTHOR]

Background Gout is the most common form of crystal arthropathy. Monoarthritis affecting the first metatarsophalangeal joint is the common initial presentation. Bilateral olecranon bursitis is a rare presentation of gout. Aim of the work To describe the clinical features of bilateral olecranon bursitis as an initial presentation of gout. Case report A 62-year old male patient presented to the rheumatology clinic , Adnan Menderes University with sudden bilateral elbow pain and swelling for three months . Swellings gradually increased to the size of a golf ball with minimal restriction in the elbow extension (170°). He didn’t have arthritis in the elbows. The patient had medical history of heart failure and chronic obstructive pulmonary disease and medications received included acetylsalicylic acid and diuretics. Blood tests revealed elevated serum uric acid (12.6 mg/dL), with normal renal function tests, erythrocyte sedimentation rate (ESR) 43 mm/h and C-reactive protein (CRP) 8.8 mg/L. Rheumatoid factor and hepatitis markers were negative. Diagnostic bursal aspiration excluded septic bursitis and under polarized microscopy monosodium urate (MSU) crystals were identified with typical negative birefringence. A diagnosis of gout was established. ESR and CRP were normalized after diclofenac potassium (100 mg) and colchicine (1.5 mg). Allopurinol 300 mg was added when his joint pain was relieved. Conclusion This is the first gout case initially presenting with bilateral olecranon bursitis. Bursal fluid analysis is important in such atypical presentation to look for MSU crystals and establish a diagnosis. [ABSTRACT FROM AUTHOR]

Crystal arthropathies are a group of joint disorders due to deposition of crystals in and around joints that lead to joint destruction and soft tissue masses. Clinical presentation is variable and diagnosis might be challenging. In this article the pathophysiology is addressed, the preferred deposition of crystal arthropathies and imaging findings. Case studies of calcium pyrophosphate dihydrate crystal deposition disease, hydroxyapatite crystal deposition disease, and gout are shown. Guidelines for the use of dual-energy computed tomography are given to enable the diagnosis and follow-up of gout., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The cervical spine is a rare site where tophaceous gout has been identified. There are currently 15 described cases in the literature of gouty involvement of the cervical spine with only three cases involving only the atlanto-axial region. We add the fourth of such cases and only the second to be managed operatively. [ABSTRACT FROM AUTHOR]

Objective. Extracellular inorganic pyrophosphate (ePPi) is a key regulator of pathologic mineralization in articular cartilage. Articular chondrocytes generate ePPi by the transportation of intracellular PPi (iPPi) through transport mechanisms such as ANK or by the degradation of extracellular adenosine triphosphate (eATP) by ectoenzymes. Although numerous modulators of ePPi have been characterized, little is known about eATP elaboration in cartilage. We sought to determine (1) whether eATP is coordinately regulated with ePPi and (2) whether ANK transports ATP. Methods. Primary articular chondrocytes were treated with factors known to modulate ePPi levels including growth factors (TGFββ1 and IGF-1), anion channel inhibitors, and chemicals that alter adenylyl cyclase and protein kinase C activities. Additional chondrocyte monolayers were infected with adenovirus containing functional (Ad-ANK) or mutated (Ad-ANK mutant) ANK sequences. eATP levels were measured with a bioluminescent assay. Results. TGFββ1 enhanced eATP accumulation by 33%%, whereas IGF-1 decreased eATP accumulation by 63%% and attenuated TGFββ1-induced eATP release by 72%%. Forskolin and probenecid diminished eATP accumulation by 55%% and 89%%. Phorbol-12-myristate-13-acetate increased eATP by 29%%. Transfection of chondrocytes with Ad-ANK caused a 10-fold increase in eATP compared with control values. Conclusion. Modulation of eATP by various factors paralleled their effects on ePPi production, suggesting a shared pathway of ePPi and eATP production and implicating ANK in eATP transport. As eATP directly contributes to pathologic mineralization in articular cartilage, understanding eATP regulation may lead to effective therapies for crystal-associated arthritis. [ABSTRACT FROM AUTHOR]

Abstract: The term ‘arthritis’ encompasses most of the pathology that causes joint symptoms or dysfunction. Arthritis can be broadly categorized into osteoarthritis, which is a degenerative disease, and inflammatory arthropathies, in which there is true inflammation of the affected joints and their associated structures. Osteoarthritis is the most common form of arthritis. It is, to an extent, part of the ageing process, but it can arise as a consequence of joint damage resulting from other diseases or injury and some individuals have an increased risk of osteoarthritis owing to hereditary factors. The management of osteoarthritis is symptomatic up to the point of serious joint dysfunction, when surgical approaches are used. Inflammatory arthropathies can be due to infection, crystal deposition within joints and their associated structures (gout, pyrophosphate arthropathy and hydroxyapatite arthropathy) or autoimmune disease. All of the autoimmune inflammatory arthropathies also have extra-articular manifestations. Rheumatoid arthritis is the most common of the inflammatory arthropathies, and is characterized by progressive, deforming inflammation of joints owing to a destructive synovitis. Another group of diseases (ankylosing spondylitis, reactive arthritis/Reiter’s syndrome, psoriatic arthritis) are characterized by enthesitis and are associated with HLA-B27. Treatment of these diseases is becoming more effective with the development of targeted biological treatments. [Copyright &y& Elsevier]

Background: Medial knee pain is a common complaint in the adult population. When conservative measures fail, intraarticular knee corticosteroid injections are often offered through the superolateral approach into the suprapatellar recess to provide short-term relief. However, some patients fail to respond and require alternative approaches. The anteromedial joint line (AMJL) approach, which targets the medial compartment, may be more effective when pain-generating pathologies such as synovitis are located in the medial compartment. To date, there have been no dedicated studies evaluating ultrasound-guided (USg) corticosteroid injections through the AMJL approach to reduce medial knee pain., Objectives: The current study aims to assess the clinical characteristics, ultrasound findings, and clinical outcomes for patients with medial knee pain who received USg corticosteroid injections via the AMJL approach., Study Design: Retrospective study., Setting: This study took place at one academic musculoskeletal ultrasound clinic at an urban tertiary care center., Methods: Sixty-five patients (76 knees; 11 patients with bilateral injections) with medial knee pain who had received USg-AMJL corticosteroid injections from January 2016 through  March 2020 were reviewed for inclusion. Baseline demographic information and clinical characteristics from one year prior to 6 months following USg-AMJL injection were analyzed for each patient. Responders were defined as those who reported pain relief, decreased usage of analgesic medications, or increased physical activity. Nonresponders  were defined as those not meeting any of the responder endpoints., Results: Within one year prior to receiving a USg-AMJL injection, 51.3% (39/76 knees) had attempted superolateral knee injections without relief. Immediately following a USg-AMJL injection, 98.7% (75/76) experienced symptomatic relief. Follow-up visits took place on average at 11 weeks postinjection with 92.3% (60/65 patients) responding positively. In comparison to the responder group, the nonresponder group had a significantly older mean age (P = 0.009), lower mean body mass index (P = 0.007), and higher burden of morbidities as measured by the Charlson Comorbidity Index (P = 0.044). One patient reported a steroid flare within one week of injection. The most common diagnoses contributing to medial knee pain for these patients were osteoarthritis, medial meniscal injury, crystal arthropathy, and medial collateral ligament injury, which were supported by point-of-care ultrasound findings., Limitations: This study was limited by its sample size and retrospective observational design., Conclusions: USg AMJL injection is a safe and effective procedure for targeting medial knee pain, particularly in the settings of obesity and prior failed superolateral and suprapatellar knee injections. Further investigation is required to assess long-term clinical outcomes of this injection approach.

Background: Craniocervical junction and subaxial cervical spinal manifestations of calcium pyrophosphate deposition disease are rarely encountered. The authors presented a severe case of retro-odontoid pseudotumor rupture causing rapid quadriparesis and an acute comatose state with subsequent radiographic and clinical improvement after posterior occipital cervical fusion., Observations: The authors surveyed the literature and outlined multiple described operative management strategies for compressive cervical and craniocervical junction calcium pyrophosphate deposition disease manifestations ranging from neck pain to paresthesia, weakness, myelopathy, quadriparesis, and cranial neuropathies. In this report, radiographic features of cervical and craniocervical junction calcium pyrophosphate deposition disease were explored. Several previously described surgical strategies were compiled, including patient characteristics and outcomes., Lessons: With this case report, the authors presented for the first time an isolated posterior occipital cervical fusion for treatment of a compressive retro-odontoid pseudotumor with rupture into the brainstem. They demonstrated rapid clinical and radiographic resolution after stabilization of cranial cervical junction only 12 weeks postsurgery.

Background: The presentation of a hot swollen joint is common in the emergency department, general practice, rheumatology and orthopedic clinics. There is a wide set of differential diagnoses for a hot swollen joint, thus making it difficult to diagnose and manage, especially for junior doctors. Initially, it is pertinent to exclude/diagnose medical and surgical emergencies., Objective: This paper aims to summarize the key indications within the history, examination and investigations in order to quickly and effectively diagnose a hot swollen joint based on the original 2006 management guidelines and the papers discussing other possible indications and management strategies published since then., Results: Currently, the management of crystal and non-infectious arthropathies is well recognized with little disparity. However, the treatment of infectious arthritis is not concrete, and there are discrepancies in management between doctors., Conclusion: We have summarized the key indications and provided a diagnostic flow chart to aid with the management of a hot swollen joint., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Gout is the most common crystal arthropathy and is frequently diagnosed and managed by primary care physicians. Point-of-care ultrasound (POCUS) is a valuable tool to aid in the diagnosis of gout via the identification of the double contour sign, aggregates of crystals, tophi, and erosions. In addition, POCUS can aid in the management of gout by recognizing early signs of gout, monitoring the effectiveness of urate-lowering therapy, and guiding aspiration and corticosteroid injection., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Espejo et al.)

Objective: To describe the characteristics of calcium pyrophosphate (CPP) crystal size and morphology under compensated polarized light microscopy (CPLM). Secondarily, to describe CPP crystals seen only with digital enhancement of CPLM images, confirmed with advanced imaging techniques., Methods: Clinical lab-identified CPP-positive synovial fluid samples were collected from 16 joint aspirates. Four raters used a standardized protocol to describe crystal shape, birefringence strength and color. A crystal expert confirmed CPLM-visualized crystal identification. For crystal measurement, a high-pass linear light filter was used to enhance resolution and line discrimination of digital images. This process identified additional enhanced crystals not seen by raters under CPLM. Single-shot computational polarized light microscopy (SCPLM) provided further confirmation of the enhanced crystals' presence., Results: Of 932 suspected crystals identified by CPLM, 569 met our inclusion criteria, and 293 (51%) were confirmed as CPP crystals. Of 175 unique confirmed crystals, 118 (67%) were rods (median area 3.6 μm 2 [range, 1.0-22.9 μm 2 ]), and 57 (33%) were rhomboids (median area 4.8 μm 2 [range, 0.9-16.7 μm 2 ]). Crystals visualized only after digital image enhancement were smaller and less birefringent than CPLM-identified crystals., Conclusions: CPP crystals that are smaller and weakly birefringent are more difficult to identify. There is likely a population of smaller, less birefringent CPP crystals that routinely goes undetected by CPLM. Describing the characteristics of poorly visible crystals may be of use for future development of novel crystal identification methods., Competing Interests: Declaration of competing interest Dr. Ozcan has a patent pending for SCPLM technology.