title: Crystal arthritides - gout and calcium pyrophosphate arthritis : Part 1: Epidemiology and pathophysiology.
abstract: Gout and calcium pyrophosphate deposition disease (CPPD, pseudogout) are still the most frequent inflammatory arthritides in multimorbid elderly patients. Gout and CPPD are different diseases and based on different pathophysiological principles. Gout is closely associated with the metabolic syndrome and is an independent risk factor for cardiovascular mortality. The prevalence of asymptomatic hyperuricemia is estimated to be 10-20% of adults in industrial nations and prevalence is strongly associated with age. More than 7% of persons aged over 65 years suffer from clinically manifest gout. The underlying pathophysiological principle is an imbalance between the formation and elimination of uric acid. The degradation of the purine bases adenine and guanosine to uric acid is catalysed by xanthine oxidase and genetic polymorphisms and mutations play an important role in absorption and excretion processes. Furthermore, carrier proteins, such as URAT-1 or OAT-4 also have an influence on these processes. An imbalance of the physiological processes results in the solubility product being exceeded, which in consequence leads to crystallization of urate. This induces a cascade of massive inflammatory reactions at the molecular and cellular level with the activation of cytokines. The inflammatory process can be stopped by neutrophil extracellular traps (NETs) that modulate aggregation and degradation of chemokines and cytokines and partitioning of crystallized urate against immune cells. Calcium pyrophosphate dehydrate (CPP) crystals are formed in the cartilage and CPP deposition can be found in 30% of people aged over 80 years. Inorganic pyrophosphate (PPi) is synthesized in chondrocytes and plays an important part in the formation of calcium pyrophosphate crystals. The degradation is catalyzed by inorganic pyrophosphatases. If there is dysregulation of this homeostasis more PPi is produced, which ultimately contributes to the formation of the CPP crystals.
authors.affiliation: Klinik für Allgemeine Innere Medizin und Geriatrie, Barmherzige Brüder Regensburg, Prüfeninger Str. 86, 93049, Regensburg, Germany. steffen.schlee@barmherzige-regensburg.de.
authors.forename: S
authors.initials: S
authors.lastname: Schlee
authors.affiliation: Lehrstuhl für Altersmedizin, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
authors.forename: L C
authors.initials: LC
authors.lastname: Bollheimer
authors.affiliation: Institut für Klinische Chemie, Laboratoriumsmedizin und Transfusionsmedizin, Klinikum Nürnberg, Paracelsus Medizinische Privatuniversität, Prof.-Ernst-Nathan-Str. 1, 90419, Nürnberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Bertsch
authors.affiliation: Klinik für Allgemeine Innere Medizin und Geriatrie, Barmherzige Brüder Regensburg, Prüfeninger Str. 86, 93049, Regensburg, Germany.|Institut für Biomedizin des Alterns, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nürnberg, Germany.
authors.forename: C C
authors.initials: CC
authors.lastname: Sieber
authors.affiliation: Klinik für Rheumatologie, Klinische Immunologie und Physikalische Therapie, Zentrum für Rheumatologische Akutdiagnostik, Katholisches Klinikum Mainz, Standort St. Vincenz und Elisabeth Hospital, An der Goldgrube 11, 55131, Mainz, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Härle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium; D002130:Calcium Phosphates / Q000009:adverse effects / Q000378:metabolism; D002131:Calcium Pyrophosphate / Q000009:adverse effects* / Q000378:metabolism; D002805:Chondrocalcinosis / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology*; D003460:Crystallization; D006073:Gout / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology*; D006801:Humans; D014527:Uric Acid
chemical_list: D002130:Calcium Phosphates; D014527:Uric Acid; D002118:Calcium; D002131:Calcium Pyrophosphate
keywords: Calcium pyrophosphate deposition disease; Elderly patients; Gout; Hyperuricemia; Uric acid crystals