Unraveling the pathological biomineralization of monosodium urate crystals in gout patients.

Crystallization of monosodium urate monohydrate (MSU) leads to painful gouty arthritis. Despite extensive research it is still unknown how this pathological biomineralization occurs, which hampers its prevention. Here we show how inflammatory MSU crystals form after a non-inflammatory amorphous precursor (AMSU) that nucleates heterogeneously on collagen fibrils from damaged articular cartilage of gout patients. This non-classical crystallization route imprints a nanogranular structure to biogenic acicular MSU crystals, which have smaller unit cell volume, lower microstrain, and higher crystallinity than synthetic MSU. These distinctive biosignatures are consistent with the template-promoted crystallization of biotic MSU crystals after AMSU at low supersaturation, and their slow growth over long periods of time (possibly years) in hyperuricemic gout patients. Our results help to better understand gout pathophysiology, underline the role of cartilage damage in promoting MSU crystallization, and suggest that there is a time-window to treat potential gouty patients before a critical amount of MSU has slowly formed as to trigger a gout flare.

Features Associated With Different Inflammatory Phenotypes of Calcium Pyrophosphate Deposition Disease: Study Using Data From the International American College of Rheumatology/EULAR Calcium Pyrophosphate Deposition Classification Criteria Cohort.

OBJECTIVE: The study objective was to examine the disease, demographic, and imaging features associated with different inflammatory phenotypes of calcium pyrophosphate deposition (CPPD) disease, ie, recurrent acute calcium pyrophosphate (CPP) crystal arthritis, chronic CPP crystal inflammatory arthritis, and crowned dens syndrome (CDS). METHODS: Data from an international cohort (assembled from 25 sites in 7 countries for the development and validation of the 2023 CPPD classification criteria from the American College of Rheumatology/EULAR) that met the criteria were included. Three cross-sectional studies were conducted to determine the phenotypic characteristics of recurrent acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and CDS. Multivariable logistic regression analysis was used to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI) to examine the association between potential risk factors and the inflammatory phenotype. RESULTS: Among the 618 people included (56% female; mean age [standard deviation] 74.0 [11.9] years), 602 (97.4%) had experienced acute CPP crystal arthritis, 332 (53.7%) had recurrent acute arthritis, 158 (25.6%) had persistent inflammatory arthritis, and 45 (7.3%) had had CDS. Recurrent acute CPP crystal arthritis associated with longer disease duration (aOR 2.88 [95% CI 2.00-4.14]). Chronic CPP crystal inflammatory arthritis was associated with acute wrist arthritis (aOR 2.92 [95% CI 1.81-4.73]), metacarpophalangeal joint osteoarthritis (aOR 1.87 [95% CI 1.17-2.97]), and scapho-trapezo-trapezoid (STT) joint osteoarthritis (aOR 1.83 [95% CI 1.15-2.91]), and it was negatively associated with either metabolic or familial risk for CPPD (aOR 0.60 [95% CI 0.37-0.96]). CDS was associated with male sex (aOR 2.35 [95% CI 1.21-4.59]), STT joint osteoarthritis (aOR 2.71 [95% CI 1.22-6.05]), and more joints affected with chondrocalcinosis (aOR 1.46 [95% CI 1.15-1.85]). CONCLUSION: CPPD disease encompasses acute and chronic inflammatory phenotypes, each with specific clinical and imaging features that need to be considered in the diagnostic workup.