Calcium pyrophosphate deposition (CPPD) disease is a consequence of the immune response to the pathological presence of calcium pyrophosphate (CPP) crystals inside joints, which causes acute or chronic inflammatory arthritis. CPPD is strongly associated with cartilage degradation and osteoarthritis, although the direction of causality is unclear. This clinical presentation is called CPPD with osteoarthritis. Although direct evidence is scarce, CPPD disease might be the most common cause of inflammatory arthritis in older people (aged >60 years). CPPD is caused by elevated extracellular-pyrophosphate concentrations in the cartilage and causes inflammation by activation of the NLRP3 inflammasome. Common risk factors for CPPD disease include ageing and previous joint injury. It is uncommonly associated with metabolic conditions (eg, hyperparathyroidism, haemochromatosis, hypomagnesaemia, and hypophosphatasia) and genetic variants (eg, in the ANKH and osteoprotegerin genes). Apart from the detection of CPP crystals in synovial fluid, imaging evidence of CPPD in joints by mainly conventional radiography, and increasingly ultrasonography, has a central role in the diagnosis of CPPD disease. CT is useful in showing calcification in axial joints such as in patients with crowned dens syndrome. To date, no treatment is effective in dissolving CPP crystals, which explains why control of inflammation is currently the main focus of therapeutic strategies. Prednisone might provide the best benefit-risk ratio for the treatment of acute CPP-crystal arthritis, but low-dose colchicine is also effective with a risk of mild diarrhoea. Limited evidence suggests that colchicine, low-dose weekly methotrexate, and hydroxychloroquine might be effective in the prophylaxis of recurrent flares and in the management of persistent CPP-crystal inflammatory arthritis. Additionally, biologics inhibiting IL-1 and IL-6 might have a role in the management of refractory disease.

This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management. New imaging tools are available, including US with key features and dual-energy CT rendering it able to reveal deposits of urate crystals. These deposits are now included in new diagnostic and classification criteria. Overall, half of the patients with gout are readily treated with allopurinol, the recommended xanthine oxidase inhibitor (XOI), with prophylaxis for flares with low-dose daily colchicine. The main management issues are related to patient adherence, because gout patients have the lowest rate of medication possession ratio at 1 year, but they also include clinical inertia by physicians, meaning XOI dosage is not titrated according to regular serum uric acid level measurements for targeting serum uric acid levels for uncomplicated (6.0 mg/dl) and complicated gout, or the British Society for Rheumatology recommended target (5.0 mg/dl). Difficult-to-treat gout encompasses polyarticular flares, and mostly patients with comorbidities, renal or heart failure, leading to contraindications or side effects of standard-of-care drugs (colchicine, NSAIDs, oral steroids) for flares; and tophaceous and/or destructive arthropathies, leading to switching between XOIs (febuxostat) or to combining XOI and uricosurics.

Introduction: The significant proportion of gout patients not reaching serum urate levels below 6.0 mg/dL and the debated pathogenicity of hyperuricemia (HU) itself motivate investigators to develop new drugs to decrease uricemia. Areas covered: This review discusses the drugs considered to be in active development from pre-clinical to phase III studies. This review covers 11 drugs in development, including a xanthine oxidase inhibitor (topiroxostat), uricosurics (verinurad, arhalofenate, UR-1102, tranilast), dual inhibitors (RLBN1001, KUX-1151), a uricase (pergsiticase), an inhibitor of hypoxanthine production (ulodesine), and drugs with yet-to-explain mechanisms of action (levotofisopam, tuna extracts). Expert opinion: Drugs well advanced in their development – particularly arhalofenate, verinurad and topiroxostat – open the prospect of patient-comorbidity-tailored HU management. Development of novel therapies provides new insight into our understanding of gout and HU, particularly potential pathogenicity. Apart from potency to decrease serum urate levels and good tolerance profiles, novel therapies will need to focus on administration modalities facilitating treatment adherence.

Objective: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first‐ever validated classification criteria for symptomatic CPPD disease.Methods: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de‐identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi‐criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort.Results: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score >56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers).Conclusion: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.