Calcium Pyrophosphate Crystal Deposition Disease Research Articles

Editorial introductions

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Kenneth SaagKenneth SaagKenneth Saag, MD, MSc, is Jane Knight Lowe Professor of Medicine, Division of Clinical Immunology and Rheumatology, at the University of Alabama at Birmingham (UAB) in Birmingham, Alabama, USA and Professor of Epidemiology, at the UAB School of Public Health. Dr Saag is a native of Chicago, and following studies in engineering at the University of Michigan, USA, he returned to Chicago for medical school and Internal Medicine Residency at Northwestern University, USA. He then traveled to the University of Iowa, USA, for his rheumatology and epidemiology training and remained on the faculty there until moving to UAB in 1998. Dr Saag is the founding Director of the Agency for Health Care Research and Quality Deep South Center for Education and Research on Therapeutics, the UAB Center of Research Translation in Gout and Hyperuricemia, and the UAB Outcomes Research Center. He also serves as a Vice Chair for the UAB Department of Medicine. He has published over 300 peer reviewed manuscripts; has also authored more than 100 reviews, editorials, and book chapters. Recently he published the first edition of the clinical handbook Diagnosis and Management of Osteoporosis. Dr Saag is the Secretary of the American College of Rheumatology (ACR) and Past President of the Board of Trustees of the National Osteoporosis Foundation. Sara K. TedeschiSara K. TedeschiDr Tedeschi is a Rheumatologist at Brigham and Women's Hospital and an Assistant Professor of Medicine at Harvard Medical School, both in Boston, Massachusetts, USA. She completed medical school at Vanderbilt University School of Medicine in Nashville, Tennessee, USA. Dr Tedeschi then completed both her internal medicine residency and rheumatology fellowship training at Brigham and Women's Hospital and received her MPH from the Harvard T.H. Chan School of Public Health. Her clinical research focuses on risk factors for and outcomes in rheumatic diseases. Dr Tedeschi's current work which focuses on calcium pyrophosphate crystal deposition disease is funded by the National Institutes of Health. She has received several prestigious awards including the Distinguished Fellow Award from the American College of Rheumatology and election to Alpha Omega Alpha. George C. TsokosGeorge C. TsokosDr George C. Tsokos, MD, is Professor of Medicine at Harvard Medical School and Chief, Rheumatology Division, Beth Israel Deaconess Medical Center in Boston, USA. He trained in Rheumatology at the National Institutes of Health, USA. He has served various leadership positions including President of the Clinical Immunology Society, Chair of the Council of the University of Athens and Member or Chair of multiple federal study sections and Editor or Member of editorial boards of scientific journals. Dr Tsokos holds a MERIT Award from the National Institutes of Health and has received several prestigious awards including the Kirkland, Howley, Evelyn Hess awards and the Distinguished Basic Investigator Award from the American College of Rheumatology, the Lupus Insight Award, the Carol Nachman International Prize in Rheumatology and the Marian Ropes Physician Achievement Award. Dr Tsokos’ laboratory has opened and led the field of molecular abnormalities on immune cells in patients with SLE and identified previously unknown pathways which have served as the basis for novel treatments which are currently in various phases of development.

Calcium pyrophosphate crystal deposition disease as a risk factor for cardiovascular diseases

Calcium pyrophosphate crystal deposition disease (CPPD) is an inflammatory joint disease associated with abnormal accumulation of inorganic pyrophosphate. CPPD is frequently associated with metabolic disorders, such as hyperparathyroidism, hemochromatosis, hypomagnesemia, and hyperphosphatasia. It is important that pathological calcification can develop in both the joints and vessel wall. It is assumed that the deposition of calcifications in the endothelium, the crystal-induced chronic inflammation characteristic of CPPD, and its accompanying oxidative stress, as well as metabolic disorders that are a cause of secondary CPPD, can significantly increase the risk of cardiovascular diseases.

Cardiovascular risk factors in patients with calcium pyrophosphate crystal deposition disease

Calcium pyrophosphate crystal deposition disease (CPCDD) is among the most common inflammatory rheumatic diseases; however, studies of cardiovascular risks in CPCDD have not been conducted. Objective : to stratify a cardiovascular risk in patients with CPCDD according to the systematic coronary risk evaluation (SCORE) algorithm that allows determination of an individual 10-year risk of cardiovascular death. Subjects and methods . The one-stage, single-center study of a cardiovascular risk enrolled 118 patients (43 men and 75 women) with CPCDD. Laboratory studies included determination of fasting serum glucose, total cholesterol, uric acid, magnesium, phosphorus, and total calcium. The level of C-reactive protein (CRP) was measured by a highly sensitive method; CRP >5 mg/L was taken as a high level; parathyroid hormone was determined by chemiluminescence immunoassay. The SCORE table was used to assess the total cardiovascular risk in all the patients. Results and discussion . The patients' mean age was 60.7±12.4 years. According to the SCORE scale, very high and high risks of cardiovascular death were found in 59 (50%) and 6 (5%) patients, respectively; only in 10% of cases this risk was associated exclusively with age (> 65 years); 60 (50.8%) of the 118 patients did not have previous cardiovascular events or atherosclerosis risk factors. Coronary heart disease was detected in 28.8% of the 118 patients; hypertension was identified in 64%; diabetes mellitus (DM) was found in almost 15%. The mean SCORE values did not signif icantly differ in men and women. The level of CRP was higher in men than that in women (8.6±4.6 and 7.3±3.5 mg/dL, respectively; p = 0.04). Glomerular filtration rate (GFR) 100 ml/min: 61% (60/98) and 25% (5/20) of patients, respectively (p = 0.003). Hyperparathyroidism (HPT) was detected in 12 (10%) patients, and 7 of them were at a very high risk by the SCORE scale; however, hypercalcemia was diagnosed in only three cases. The results of the SCORE stratification of the whole group showed that 64 (54.2%) of the 118 patients with CPCDD were at a very high or high risk, the latter was very high in exactly half of the cases (n = 59. Conclusion . One-half of patients with CPCDD have a very high cardiovascular risk. In addition to the high detection rate of traditional cardiovascular risk factors (hypertension, smoking, hypercholesterolemia, and DM), the presence of chronic microcrystalline inflammation, concomitant metabolic disorders and diseases (hyperuricemia, HPT, decreased renal function) should be taken into account when determining the cardiovascular risk in patients with CPCDD.

Experience with methotrexate in a patient with calcium pyrophosphate crystal deposition disease

The paper discusses the results of using methotrexate (MTX) in real clinical practice in a patient with calcium pyrophosphate crystal deposition resistant to traditional anti-inflammatory drugs (colchicine, nonsteroidal anti-inflammatory drugs, and hydroxychloroquine) It demonstrates the efficiency and possibility of safely using MTX at a dose of 20 mg/week during a year.

Current strategy in the treatment of calcium pyrophosphate crystal deposition disease

The paper considers currently available drugs used to treat calcium pyrophosphate crystal deposition disease. It discusses the advantages and disadvantages of the most widely used drugs, such as nonsteroidal anti-inflammatory drugs, colchicine, glucocorticoids, traditional immunosuppressants, as well as prospects for the use of biologic agents.

Crowned dens syndrome: a case report followed by an update on differential diagnosis and treatment

Introduction Crowned dens syndrome (CDS) is a rare clinical presentation of chondrocalcinosis or calcium pyrophosphate crystal deposition (CPPD) disease, characterized by fever, neck pain and stiffness, associated with increased biological markers of inflammation. Diagnosis is made mainly via imaging, and the best modality remains the magnetic resonance imaging (MRI) of the neck showing calcification and calcium pyrophosphate crystals deposition around the odontoid process (1). The aim of this report is to increase awareness of this rare and ill-known clinical tableau and to review its complications and the latest modalities of its diagnosis and treatment. Clinical case: An 83-year-old female patient presented to the emergency department (ED) of the Middle East Institute of Health (MEIH) with severe acute onset neck stiffness and pain of 10/10 intensity, radiating to the submandibular area and reaching the occipital part of the head, associated with nausea and 2 episodes of chills one day prior to presentation. Patient denied any recent history of trauma or surgery of the head and neck. Physical exam at that time was only remarkable for marked limitation of neck motion, and positive Kernig and Brudzinski signs. No skin changes, facial sinuses tenderness, cervical lymphadenopathies or neck swellings were noted. Vital signs at ED were within normal range except for a low grade fever. Laboratory work-up upon presentation showed hyperleukocytosis (WBC = 14000/mm3) with left shift and a C-reactive protein (CRP) of 189 mg/L (0-5 mg/L). Chest X-Ray only showed degenerative osteoarthritis of the thoracic spinal vertebrae. CT-scan of the brain without IV contrast done urgently showed no acute changes. As Clinical and biological features were suggestive of acute meningitis, cultures were taken including blood, urine and CSF fluid from lumbar puncture. The patient was admitted to the hospital for IV antibiotic treatment with a large spectrum carbapenem and close observation. On next 2 days, the patient continued to develop low grade fever with a fluctuating pattern, and levofloxacin and amikacin shots were added for maximal bacterial coverage. Urine and blood culture yielded positive for Escherichia Coli only resistant to penicillin. CSF fluid analysis and culture was unremarkable. So, the patient continued to receive IV antibiotics for urinary tract infection and bacteremia. And although the cultures were sensitive to the antibiotics given, the patient continued to suffer from fever, headache, neck stiffness with minimal improvement and response to IV acetaminophen. Laboratory markers continued to increase and CRP reached 325. The patient then underwent a series of imaging and laboratory tests to determine the cause of fever, including CT-scan of the chest, abdomen and pelvis with IV contrast, widal, wright, Rose Bengal, stool analysis, stool culture, clostridium difficile toxins, transthoracic and transesophageal cardiac ultrasound that were all negative. Finally, neck MRI was done to rule out spondylodiscitis or a cervical abscess and showed evidence of osteoarthritis on multiple cervical spinal levels, calcification of the odontoid process of C2, and thickening of the synovium and posterior ligaments (Fig C – D). Those results were compatible with a CT-scan of the neck then done and was in favor of a corona of calcification around the odontoid process suggesting a crowned dens syndrome (Fig A – B). The patient was put on colchicine therapy, and started to improve slowly, then corticosteroids were added and yielded a faster improvement. The C-reactive protein finally started to drop until reaching 23 mg/L upon the discharge. The patient was finally discharged on NSAIDs and colchicine. And after 1 month, the patient was seen in an outpatient setting where she reported dramatic improvement of her symptoms.

Review: Unmet Needs and the Path Forward in Joint Disease Associated With Calcium Pyrophosphate Crystal Deposition

Calcium pyrophosphate (CPP) crystal deposition (CPPD) is prevalent and can be associated with synovitis and joint damage. The population of elderly persons predominantly affected by CPPD is growing rapidly. Since shortfalls exist in many aspects of CPPD, we conducted an anonymous survey of CPPD unmet needs, prioritized by experts from the Gout, Hyperuricemia and Crystal-Associated Disease Network. We provide our perspectives on the survey results, and we propose several CPPD basic and clinical translational research pathways. Chondrocyte and cartilage culture systems for generating CPP crystals invitro and transgenic small animal CPPD models are needed to better define CPPD mechanism paradigms and help guide new therapies. CPPD recognition, clinical research, and care would be improved by international consensus on CPPD nomenclature and disease phenotype classification, better exploitation of advanced imaging, and pragmatic new point-of-care crystal analytic approaches for detecting CPP crystals. Clinical impacts of CPP crystals in osteoarthritis and in asymptomatic joints in elderly persons remain major unanswered questions that are rendered more difficult by current inability to therapeutically limit or dissolve the crystal deposits and assess the consequent clinical outcome. Going forward, CPPD clinical research studies should define clinical settings in which articular CPPD does substantial harm and should include analyses of diverse clinical phenotypes and populations. Clinical trials should identify the best therapeutic targets to limit CPP crystal deposition and associated inflammation and should include assessment of intraarticular agents. Our perspective is that such advances in basic and clinical science in CPPD are now within reach and can lead to better treatments for this disorder.

USE OF METHOTREXATE IN PATIENTS WITH CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION DISEASE

Objective: to compare the efficacy of methotrexate (MTX) and colchicine in patients with chronic arthritis in calcium pyrophosphate crystal deposition disease (CPPDD). Subjects and methods . Data from a controlled prospective cross-sectional study of 10 patients (8 women and 2 men) with chronic arthritis in CPPDD are presented. In the initial period of treatment, all the patients were given colchicine 1 mg/day for 3 months, followed by a wash-out period for 1 month and then subcutaneous MTX 20 mg/week for 3 months. The diagnosis of CPPDD was made if there were calcium pyrophosphate crystals in synovial fluid and signs of chondrocalcinosis, as evidenced by joint X-ray and/or ultrasonography. DAS44, the swollen joint count (SJC) and tender joint count (TJC), pain intensity on a visual analog scale (VAS), the Health Assessment Questionnaire (HAQ) index, and serum C-reactive protein (CRP) levels were determined in all the patients at baseline, 3 months after the beginning of treatment with colchicine, after a wash-out period, and 3 months after the beginning of MTX treatment. Results and discussion . At baseline, mean DAS44 value was 2.47±0.27; SJC and TJC were 2.0±0.6 and 2.4±1.1, respectively; pain intensity was 55.2±12.3 mm; serum CRP level – 3.89±3.82 mg/l; HAQ – 1.1±0.3. Three months after colchicine therapy initiation, mean DAS44 value decreased to 1.76±0.28 (p = 0.004), SJC – to 1.4±0.5 (p = 0.048), TJC – to 1.6±1.35 (p = 0.023), pain intensity – to 42.0±13.2 mm (p = 0.023), CRP level – to 3.13±2.85 mg/l (p = 0.75), HAQ – to 0.95±0.3 (p = 0.041). Good response was achieved in 7 patients after 3 months of colchicine therapy. After the wash-out period, the mean DAS44 value was 2.08±0.26; SJC and TJC – 1.6±0.5 and 1.7±1.4, respectively; pain intensity – 46.5±9.8 mm; CRP level – 3.38±1.74 mg/l; HAQ – 1.3±0.34. Following 3 months of MTX therapy, mean DAS44 value decreased to 1.39±0.45 (p = 0.027), SJC – to 0.7±0.5 (p = 0.023), TJC – to 0.6±0.5 (p = 0.007), pain intensity – to 26.0±18.97 mm (p = 0.045), CRP level – to 2.87±2.06 mg/l (p = 0.75), HAQ – to 0.8±0.6 (p = 0.045). Two of the 3 patients with an insufficient effect of colchicine achieved DAS44 remission after MTX treatment; two patients attained remission after therapy with colchicine and developed an exacerbation of the disease when this drug was replaced by MTX. Conclusion. MTX 20 mg/week is as effective as colchicine in most cases and can be the drug of choice in patients with chronic arthritis in CPPDD if colchicine therapy is ineffective.

Colchicine treatment in adult patients with knee osteoarthritis: Systematic review of the literature

Abstract Background Colchicine is often used in patients with osteoarthritis in which calcium pyrophosphate crystal deposition disease is suspected. Colchicine has also been used by many rheumatologists in clinical practice, and in some trials, on patients with primary osteoarthritis (apparently unrelated to calcium pyrophosphate). However, its role in the treatment of primary osteoarthritis is not clear, and international guidelines have not established recommendations. Objective To evaluate the efficacy and safety of colchicine for the treatment of adult patients with primary knee osteoarthritis as well as the form associated with calcium pyrophosphate. Methods A structured literature search was conducted using the PubMed, Embase, Cochrane Controlled Trials Register, and LILACS databases. Randomized controlled trials were included in which colchicine was used as intervention in patients with primary or pyrophosphate calcium-associated knee osteoarthritis. Results The study included 5 randomized controlled trials, all of which showed a common trend in all estimated points of the joint, favoring the use of colchicine for improvement in pain and functionality. Although the effect was not statistically significant in individual studies, there was a greater tendency of gastrointestinal adverse effects with the use of colchicine. None of the studies assessed quality of life. Conclusions Colchicine appears to be an effective and safe alternative for treatment of adult patients with knee osteoarthritis, either primary or associated with the deposit of calcium pyrophosphate crystals. Its use reduces pain and improves functionality, but it can cause gastrointestinal symptoms in some patients.

Revisión sistemática de la literatura sobre el tratamiento con colchicina en pacientes adultos con osteoartritis de rodilla

BackgroundColchicine is often used in patients with osteoarthritis in which calcium pyrophosphate crystal deposition disease is suspected. Colchicine has also been used by many rheumatologists in clinical practice, and in some trials, on patients with primary osteoarthritis (apparently unrelated to calcium pyrophosphate). However, its role in the treatment of primary osteoarthritis is not clear, and international guidelines have not established recommendations. ObjectiveTo evaluate the efficacy and safety of colchicine for the treatment of adult patients with primary knee osteoarthritis as well as the form associated with calcium pyrophosphate. MethodsA structured literature search was conducted using the PubMed, Embase, Cochrane Controlled Trials Register, and LILACS databases. Randomised controlled trials were included in which colchicine was used as intervention in patients with primary or pyrophosphate calcium-associated knee osteoarthritis. ResultsThe study included 5 randomised controlled trials, all of which showed a common trend in all estimated points of the joint, favouring the use of colchicine for improvement in pain and functionality. Although the effect was not statistically significant in individual studies, there was a greater tendency of gastrointestinal adverse effects with the use of colchicine. None of the studies assessed quality of life. ConclusionsColchicine appears to be an effective and safe alternative for treatment of adult patients with knee osteoarthritis, either primary or associated with the deposit of calcium pyrophosphate crystals. Its use reduces pain and improves functionality, but it can cause gastrointestinal symptoms in some patients.

Systematic review and quality analysis of emerging diagnostic measures for calcium pyrophosphate crystal deposition disease

ObjectivesCalcium pyrophosphate crystal deposition disease (CPPD) is common, yet prevalence and overall clinical impact remain unclear. Sensitivity and specificity of CPPD reference standards (conventional crystal analysis (CCA) and radiography (CR))...

Immobilization of inorganic pyrophosphatase on nanodiamond particles retaining its high enzymatic activity.

Nanodiamond (ND) particles are popular platforms for the immobilization of molecular species. In the present research, enzyme Escherichia coli inorganic pyrophosphatase (PPase) was immobilized on detonation ND through covalent or noncovalent bonding and its enzymatic activity was characterized. Factors affecting adsorption of PPase such as ND size and surface chemistry were studied. The obtained material is a submicron size association of ND particles and protein molecules in approximately equal amounts. Both covalently and noncovalently immobilized PPase retains a significant enzymatic activity (up to 95% of its soluble form) as well as thermostability. The obtained hybrid material has a very high enzyme loading capacity (∼1 mg mg(-1)) and may be considered as a promising delivery system of biologically active proteinaceous substances, particularly in the treatment of diseases such as calcium pyrophosphate crystal deposition disease and related pathologies. They can also be used as recoverable heterogeneous catalysts in the traditional uses of PPase.

THE CLINICAL MANIFESTATIONS OF CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION DISEASE

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SAT0510 Ultrasound versus Synovial Fluid Analysis for the Diagnosis of Calcium Pyrophosphate Dihydrate Deposition Disease: is IT Cppd? Ask Us!

BackgroundThe diagnosis of calcium pyrophosphate crystal (CPP) deposition disease (CPPD) is mainly based on the synovial fluid analysis and Xrays. US has demonstrated high sensitivity and specificity values for diagnosing...

SAT0382 Arthrosonographic Findings in Crystal Arthropathies

BackgroundAt the time, crystal arthropathies (CA) (e.g. calcium pyrophosphate crystal deposition disease (CPPD) and gout (GA)) can be diagnosed definitely only by microscopic investigation of joint effusion with polarisation filter,...

FRI0501 Ultrasound versus synovial fluid analysis for the diagnosis of calcium pyrophosphate dihydrate deposition disease: preliminary results.

BackgroundThe diagnosis of calcium pyrophosphate crystal (CPP) deposition disease (CPPD) is mainly based on the synovial fluid analysis and Xrays. US has demonstrated high sensitivity and specificity values for diagnosing...

Tumoral Calcinosis Form of Hydroxyapatite Deposition Disease in Related Red-Bellied Short-Necked Turtles, Emydura subglobosa

Ten of 12 red-bellied short-necked turtles from a single clutch presented at 9 months of age with multiple white to tan nodules on their feet. Histologically, the nodules were composed of large periarticular deposits of mineralized crystalline material that extended into the joint spaces of interphalangeal joints and was surrounded by granulomatous inflammation and fibrosis. Crystallographic analysis determined the material to be apatite (calcium phosphate hydroxide) consistent with the tumoral calcinosis form of hydroxyapatite deposition disease (HADD). HADD has previously been described in aquatic turtles and rarely lizards and must be differentiated from gout in reptiles. A cause for the tumoral calcinosis lesions in these turtles could not be determined; however, based on previous reports in this species, a species-specific predilection, in conjunction with unknown environmental factors, is suspected. The use of the terms HADD, pseudogout (calcium pyrophosphate crystal deposition disease), and calcinosis circumscripta has been inconsistent, creating confusion in the literature.

OSTEOPOROSIS IN CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION DISEASE

Objective: to study the incidence of osteoporosis (OP) in patients with calcium pyrophosphate crystal deposition disease (CPCDD). Subjects and methods. Eighty patients with CPCDD were examined. Bone mineral density (BMD) of the forearm, lumbar spine, and femoral neck was determined by dual-energy X-ray absorptiometry. Laboratory diagnosis involved determination of the blood levels of C-reactive protein, parathyroid hormone, calcium, magnesium, and phosphorus and the daily urinary excretion of calcium and phosphates. Results. The patients with OP were significantly older than those with normal BMD and osteopenia. Forearm bones were the most common isolated location of OP and osteopenia. Injuries in the history, traumatic fractures, and the intake of diuretics were somewhat more common in the patients diagnosed with OP. The incidence of hyperparathyroidism did not differ significantly in the groups.

Do Not Hallow until You Are out of the Wood! Ultrasonographic Detection of CPP Crystal Deposits in Menisci: Facts and Pitfalls

Purpose. Ultrasonography (US) has been demonstrated to be an important tool in the diagnosis of calcium pyrophosphate (CPP) crystal deposition disease. The aim of our study was to individuate and describe possible pitfalls in US detection of such deposits in menisci. Patients and Methods. We enrolled all patients waiting to undergo knee replacement surgery due to osteoarthritis, for one-month period. Each patient underwent US examination of the knee, focusing on the menisci. After surgery, the menisci were examined by US, macroscopically and microscopically, using the microscopic analysis as the gold standard for CPP deposition. Results. 11 menisci of 6 patients have been studied. Ex vivo examination of menisci performed better in CPP identification than in vivo examination. The possible reasons of misinterpretation or misdiagnosis of the in vivo exam were identified and are extensively described in the paper. Also a new sign of CPP crystal deposits was found. Conclusions. This study permitted to highlight some difficulties in CPP crystal detection by US in menisci. Further studies are needed to define completely US CPP crystal aspect and to improve the sensibility and specificity of US in CPP deposition diagnosis.

Treatment of hyperuricemia, gout and other crystalline arthritidies

Gout is a very common joint disease which is due to chronic hyperuricemia and its related articular involvements. Yet it can be cured when appropriately managed. Comprehensive management of gout involves correct identification and addressing all causes of hyperuricemia, treating and preventing attacks of gouty inflammation (using colchicine NSAIDs, and/or steroids), and lowering serum urate (SUA) to an appropriate target level indefinitely. The ideal SUA target is, at a minimum, less than 6 mg/dL (60 mg/L or 360 μmol/L), or even less than 5 mg/dL in patients with tophi. The SUA target should remain at less than 6 mg/dL for long in all gout patients, especially until tophi have resolved. Patient education and adherence to therapy are key point to the optimal management of gout, aspects which are often neglected. Adherence can be monitored in part by continuing, regular assessment of the SUA level. More difficult cases of gout often need a combination of urate lowering therapy (ULT) for both refractory hyperuricemia and chronic tophaceous arthritis. Chronic tophaceous gouty arthropathy which do not respond adequately to optimized oral ULT might benefit from the use of pegloticase, when this is available in, for example, Italy and other European countries. By contrast, in calcium pyrophosphate (CPP) crystal deposition disease (CPPD), as evidenced by pseudo gout attacks or chronic polyarthritis, similar anti-inflammatory strategies have been recommended, but there have as yet been no controlled trials. Of note, there is no treatment for the underlying metabolic disorders able to control the CPPD. Management of crystal-induced arthropathies (CIA) depends not only on clinical expression, namely acute attacks or chronic arthropathy, but also on the underlying metabolic disorder. We will mainly focus on gout as an archetype of CIA.