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Objectives Arterial calcification due to deficiency of CD73 (ACDC) is a hereditary autosomal recessive ectopic mineralization syndrome caused by loss-of-function mutations in the ecto-5′-nucleotidase gene. Periarticular calcification has been reported but the clinical characterization of arthritis as well as the microstructure and chemical composition of periarticular calcifications and SF crystals has not been systematically investigated. Methods Eight ACDC patients underwent extensive rheumatological and radiological evaluation over a period of 11 years. Periarticular and synovial biopsies were obtained from four patients. Characterization of crystal composition was evaluated by compensated polarized light microscopy, Alizarin Red staining for synovial fluid along with X-ray diffraction and X-ray micro tomosynthesis scanner for periarticular calcification. Results Arthritis in ACDC patients has a clinical presentation of mixed erosive-degenerative joint changes with a median onset of articular symptoms at 17 years of age and progresses over time to the development of fixed deformities and functional limitations of small peripheral joints with, eventually, larger joint and distinct axial involvement later in life. We have identified calcium pyrophosphate and calcium hydroxyapatite (CHA) crystals in SF specimens and determined that CHA crystals are the principal component of periarticular calcifications. Conclusion This is the largest study in ACDC patients to describe erosive peripheral arthropathy and axial enthesopathic calcifications over a period of 11 years and the first to identify the composition of periarticular calcifications and SF crystals. ACDC should be considered among the genetic causes of early-onset OA, as musculoskeletal disease signs may often precede vascular symptoms. [ABSTRACT FROM AUTHOR]

Objectives Microcrystal-induced arthritis is still an unresolved paradigm for medicine. Overt inflammation may be absent even when crystals occur in SF. Recently, the production of neutrophil extracellular traps (NETs) embedding MSU crystals has been proposed as a possible mechanism of the auto-resolution of the inflammatory phase during gout. We aimed to verify and quantify the release of NETs in SFs during gout and pseudogout attacks and to compare any differences with respect to crystals and neutrophils number, and to analyse activation of necroptosis pathway in SF from crystal-induced arthritis. Methods SF samples were obtained by arthrocentesis from 22 patients presenting acute crystal-induced arthritis, gout or pseudogout (n  = 11 each group), and from 10 patients with acute non-crystal arthritis as controls. NETosis was quantified in SF by nucleic acid stain and by quantification of human neutrophil elastase. Activation of phosphorylated MLKL was assessed by western blot. Results We observed that SF neutrophils encountering MSU and CPPD crystals during episodes of gout and pseudogout release NETs in relation to the number of crystals in SF and irrespective of neutrophil density and type of crystal. This release was accompanied by necroptosis through the activation of the MLKL pathway. Conclusions Our findings suggest that a role of NETs in crystal-induced arthritis is to 'trap extracellular particles', including microcrystals. Embedding crystals in aggregates of NETs may be the basis of tophi and CPPD deposition, and may have implications for disease evolution rather than for spontaneous resolution of the acute attack. [ABSTRACT FROM AUTHOR]

Objective We aimed to determine whether calprotectin and α-defensins could discriminate septic from other inflammatory arthritides. Methods Synovial fluids with a predominance of neutrophils from patients with septic arthritis, pseudogout and RA were prospectively collected. Neutrophil-related proteins calprotectin and human neutrophil α-defensins levels were assessed in synovial fluids. Demographic parameters and biomarkers with P -value ⩽0.05 for differentiating septic from non-septic arthritis were included in a multivariable model. Multivariable logistic regression with stepwise selection was performed to build the final combined model. Results A total of 74 patients were included: septic arthritis (n = 26), pseudogout (n = 28) and RA (n = 20). Patients with septic arthritis were more likely to be male and young, and to display higher synovial neutrophil count. Calprotectin was significantly increased in patients with septic arthritis. The multivariable model included calprotectin, synovial fluid neutrophil count and gender. Calprotectin was the only biomarker that discriminated septic arthritis from non-septic inflammatory arthritides, with 76% sensitivity, 94% specificity and a positive likelihood ratio = 12.2 at the threshold for calprotectin of 150 mg/l. Conclusion Synovial fluid calprotectin is a relevant biomarker to discriminate septic arthritis from other inflammatory arthritides. This biomarker should be tested in an independent cohort. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the association between the purported risk factors for chondrocalcinosis and gout and the risk of pseudogout in the general population.Methods. We conducted a case–control study nested within a UK general practice database (The Health Improvement Network) by identifying incident cases of pseudogout between 1986 and 2007 and up to 10 control subjects matched to each case, based on age, sex and follow-up time. We evaluated the purported risk factors for chondrocalcinosis (i.e. OA, RA, hyperparathyroidism and diuretics) and established risk factors for gout (as comparison exposures) using conditional logistic regression analysis.Results. We identified 795 cases of pseudogout and 7770 matched control subjects. The risk of pseudogout was associated with hyperparathyroidism [odds ratio (OR) 4.87; 95% CI 2.10, 11.3], OA (OR 2.91; 95% CI 2.48, 3.43) and loop diuretic use (OR 1.35; 95% CI 1.09, 1.67). RA, thiazide diuretic use, BMI and other gout risk factors were not associated with the risk of pseudogout, except for chronic renal failure (OR 2.29; 95% CI 1.30, 4.01).Conclusion. This general population study based on physician-recorded pseudogout suggests that most of the previously observed associations with chondrocalcinosis are replicable with the risk of pseudogout, but there are notable differences, such as thiazide diuretics, RA and chronic renal failure, highlighting the need to study the clinical outcome, pseudogout. Avoiding loop diuretics may help individuals with recurrent pseudogout. [ABSTRACT FROM PUBLISHER]