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Objectives: To investigate the diagnostic accuracy of ultrasound and conventional radiography in the evaluation of calcium pyrophosphate crystal deposits at wrist level.Methods: Consecutive patients with a "definite" diagnosis of calcium pyrophosphate deposition disease and disease-controls were prospectively included in this cross-sectional single-centre study. Scapho-lunate ligament, triangular fibrocartilage complex, and volar recess of the radio-lunate joint were explored using ultrasound, conventional radiography and computed tomography.Results: Sixty one patients and 39 disease controls were enrolled. Two-hundred wrists were evaluated using both conventional radiography and ultrasound and 26 using computed tomography. Ultrasound findings indicative of crystal deposits were found in at least one wrist in 95.1% of patients and in 15.4% of controls (P<0.001). Scapho-lunate ligament calcifications were reported in 83.6% of patients and in 5.1% of controls (P<0.001). On conventional radiography, calcifications were found in at least one wrist in 72.1% of patients and in 0% of controls (P<0.001). Using the Ryan-McCarty criteria as a gold standard, sensitivity, specificity and diagnostic accuracy were 0.72 (0.59-0.83), 1.0 (0.91-1.0) and 0.83 (0.74-0.90) for conventional radiography and 0.95 (0.86-0.99), 0.85 (0.69-0.94) and 0.91 (0.84-0.96) for ultrasound. The agreement between ultrasound and computed tomography was substantial when assessing triangular fibrocartilage complex (kappa=0.70; 0.43-0.97) and scapho-lunate ligament (kappa=0.69; 0.41-0.97), and moderate for radio-lunate joint (kappa=0.46; 0.12-0.80).Conclusions: This study supports the diagnostic accuracy of ultrasound in evaluating wrist involvement in calcium pyrophosphate deposition disease. The inclusion of the scapho-lunate ligament in a disease-oriented scanning protocol could improve the diagnostic performance of ultrasound. [ABSTRACT FROM AUTHOR]

Objective: Ultrasound (US) seems a useful tool for diagnosis of calcium pyrophosphate (CPP) deposition (CPPD). We aimed to compare the performance of US and conventional radiography of the wrist for diagnosis of CPPD.Methods: Patients with CPP crystals identified in synovial fluid (SF) (knee, hip, shoulder, ankle or wrist) were consecutively included and compared to patients without CPP crystals in synovial fluid considered as controls. As recommended, we used the term chondrocalcinosis (CC) to assess imaging features suggesting CPPD. In all patients, US and radiographic assessment of CC of the wrists was performed by two distinct operators blinded each other (one operator by imaging modality). The two operators were blinded to clinical data, SF analysis and US or radiography findings.Results: We included 32 CPPD patients and 26 controls. Among CPPD patients, US revealed CC in 30 (93.7%) and radiography in 17 (53.1%) (P<0.001). The sensitivity and specificity of US for the diagnosis of CPPD were 94% and 85%, respectively; the positive likelihood ratio (LR+) was 6.1. The sensitivity and specificity of radiography were 53.1% and 100%, respectively. At joints level independently of SF analysis, US revealed CC in 35 joints without radiographic CC whereas X-rays showed CC in 3 joints without US CC. The κ coefficient between US and radiography for CC was moderate: 0.33 (0.171-0.408).Conclusion: Our study suggests that wrist US should be considered as a relevant tool for the diagnosis of CPPD, with higher sensitivity than radiography for detecting CPP deposits. [ABSTRACT FROM AUTHOR]

Joint fluid analysis must be performed as part of the diagnostic workup for acute arthritis, most notably to rule out septic arthritis and to allow the identification of crystal-induced arthritis (gout or calcium pyrophosphate deposition disease), which is one of the most common causes. However, the detection of monosodium urate or calcium pyrophosphate microcrystals is not the only goal of the polarized light microscopy examination of joint fluid. Other, less common microcrystals may be found. Among them are phospholipid microspherules, which are easily recognized microscopically based on their Maltese cross-like appearance. Phospholipid microspherules are a cause of acute arthritis that is often missed by rheumatologists and may therefore be more common than generally believed. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of combined cytology and microcrystal detection in joint fluid for diagnosing septic arthritis.Methods: Retrospective single-center study of joint fluid samples from patients with manifestations suggesting acute or chronic arthritis. The absolute leukocyte count (/mm3) was recorded; as well as the differential counts, particularly of neutrophils (%). Microcrystals were sought and bacteriological cultures performed. Septic arthritis was defined as positive cultures of joint fluid or blood samples. Diagnostic performance was assessed based on sensitivity, specificity, the receiver-operating characteristics (ROC) curve with the area under the curve (AUC), and the positive and negative likelihood ratios (LR+ and LR-).Results: Two hundred and eight joint fluid samples were included. The diagnoses were septic arthritis (n=28), chondrocalcinosis (n=41), gout (n=28), rheumatoid arthritis (n=33), spondyloarthritis (n=31), osteoarthritis (n=18), and undifferentiated arthritis (n=29). Among cytological parameters, those having the best diagnostic performance were the neutrophil count (cutoff, >50,000/mm3), the leukocyte count (cutoff, >50,000/mm3), and the percentage of neutrophils (cutoff, >95%); corresponding LR+ values were 8.93, 5.76, and 4.55, respectively. Neutrophil percentages lower than 80% had an LR- value of 0.07. Combining these cytological variables with the absence of crystals improved the diagnostic performance, yielding LR+ values of 11.36, 10.94, and 10.82 for neutrophils >95%, neutrophils >50,000/mm3, and leukocytes >50,000/mm3, respectively.Conclusion: Combining cytological characteristics of joint fluid with the absence of crystals benefits the diagnosis of septic arthritis. [ABSTRACT FROM AUTHOR]

Objectives: To describe the occurrence in prosthetic joints of crystal-induced arthritis (CIA) defined as the deposition within the synovial membrane and/or joint cavity of calcium pyrophosphate dehydrate (CPPD) (chondrocalcinosis), sodium urate (gout), or hydroxyapatite.Methods: We retrospectively reviewed the 7 cases of prosthetic-joint CIA seen between 1993 and 2013 at a medical-surgical center specialized in the management of osteoarticular infections.Results: The 4 females and 3 males ranged in age from 67 to 79 years. Acute CIA occurred at the knee in 6 patients (5 with total knee arthroplasty and 1 with unicompartmental knee arthroplasty) and at the hip in 1 patient (with total hip arthroplasty). Time from arthroplasty to CIA varied from 7 days to 9 years. An abrupt onset was a consistent feature, with pain, complete loss of function, and local evidence of inflammation. A single patient had a fever and 6 patients had laboratory evidence of systemic inflammation. Joint aspiration showed hemarthrosis in 3 patients and inflammatory joint fluid with 20,000 to 79,000neutrophils/mm(3) in 6 patients. Joint fluid cultures were negative in 6 patients. CPPD crystals were evidenced in 5 patients, including 1 who also had hydroxyapatite crystals detected by electron microscopy after alizarin red staining. Monosodium urate crystals were found in 1 patient. The remaining patient had both CPPD crystals and positive cultures for Campylobacter fetus. In 5 patients, treatment with colchicine or a nonsteroidal antiinflammatory drug ensured prompt control of the symptoms and systemic inflammation. The patient with total hip arthroplasty underwent joint aspiration for hemarthrosis. In 1 patient, an intraarticular injection of triamcinolone hexacetonide improved the symptoms and systemic inflammation. The patient with Campylobacter fetus infection was treated with antibiotics, excision of the abscess, and synovectomy.Conclusion: CIA may occur after arthroplasty, within synovial membrane remains or neosynovium developed around the prosthetic joint. CIA is a manifestation of a metabolic disease that persists and can reactivate after surgery. Routine testing for crystals is rarely performed in patients with sterile arthritis of a prosthetic joint, and crystals are difficult to detect in joints with hemarthrosis; consequently, the frequency of prosthetic-joint CIA may be underestimated. Although rare, CIA should be considered routinely when symptoms suggesting septic arthritis develop in a prosthetic joint, in order to avoid unnecessary prolonged antibiotic therapy and, in some cases, surgery. The treatment is usually simple. [ABSTRACT FROM AUTHOR]

Objective: To describe the hospital burden of microcrystal arthropathies in France.Methods: Data were extracted from the 2009-2011 French hospital national databases. We selected all hospital stays for microcrystal arthropathies (gout, chondrocalcinosis, other) encoded as primary or secondary diagnoses in patients older than 18. A descriptive analysis focused on number of patients and hospital stays, age, gender, comorbidities related to metabolic syndrome, and hospital costs based on 2012 public-sector costs.Results: 132,275 hospitalizations involving 109,734 patients were related to microcrystal arthropathies encoded as primary or secondary diagnosis (61% related to gout, 34% to chondrocalcinosis, and 5% to other microcrystal arthropathies). 23,362 hospitalizations involving 25,105 patients were due to microcrystal diseases, encoded as primary diagnosis, (48% related to gout, 43% to chondrocalcinosis, and 9% to other microcrystal arthropathies). In this population, patients with chondrocalcinosis were older (mean 75.6±13.5 versus 71±16 years for other microcrystal arthropathies and 69.7±14.7 for gout). Men represented 70% of the patients with gout, 39% of those with chondrocalcinosis and 52% of the patients with other microcrystal arthropathies. Hypertension, diabetes, dyslipidemia, cardiac ischemia, and renal failure were more frequent in patients with gout than other patients. The hospital costs for microcrystal arthropathies encoded as primary diagnosis were 82.3 million Euros, 45% related to gout, 45% to chondrocalcinosis and 11% to other microcrystals.Conclusion: In terms of hospital costs, gout and chondrocalcinosis represented the main part of the economic burden of crystal arthropathies and a high level of diseases belonging to the metabolic syndrome. Specific education programs favouring accurate microcrystal diagnosis and adherence to treatment could diminish this hospital economic burden. [ABSTRACT FROM AUTHOR]

Objectives To assess the diagnosis usefulness of fresh joint fluid analysis by the rheumatologist. Methods Prospective single-center 1-year study at a university hospital in Rennes, France. A rheumatologist determined whether the freshly collected fluid suggested a mechanical or inflammatory condition and contained monosodium urate (MSU) and/or calcium pyrophosphate (CCP) microcrystals. Agreement between the rheumatologist results and laboratory results was assessed based on the kappa coefficient (κ). We then determined the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of joint fluid analysis by the rheumatologist and by the laboratory, using the final diagnosis based on the full set of clinical, laboratory, and imaging findings as the reference standard. Results We included 180 joint fluid samples. The κ values were 0.80 for mechanical or inflammatory fluid, 0.97 for presence of MSU microcrystals, and 0.69 for presence of CCP microcrystals. The rheumatologist findings had 94.2% sensitivity and 84.6% specificity for inflammation; corresponding values were 80.7% and 100% for MSU microcrystals and 66.7% and 93.2% for CCP microcrystals. Conclusion Fresh joint fluid examination by the rheumatologist shows good to excellent agreement with the laboratory analysis for determination of the mechanical or inflammatory nature of the fluid and for detection of MSU and CCP microcrystals. [ABSTRACT FROM AUTHOR]

Objective: Hypersensitivity to vitamin D (HVD) due to a loss of function mutation of the CYP24A1 gene, which encodes vitamin D catabolizing enzyme was initially described as a cause of acute hypercalcemia in children and chronic renal diseases in adults.Methods: We describe the first case of a patient presenting a calcium pyrophosphate deposition disease (CPDD) revealing a HVD.Results: An abnormality of phospho-calcic metabolism was discovered during the course of an etiological workup for CPDD in a 52-year-old patient. Laboratory tests revealed a blood calcium level at the upper limit of normal range, a markedly low parathormone level, a 25-hydroxyvitamin D level within the upper level of normal, an elevated 1,25-dihydroxyvitamin D level and an elevated urine calcium level. CYP24A1 gene sequencing analysis revealed two mutations in a heterozygous state. The study of the 25-hydroxyvitamin D3: 24,25-dihydroxyvitamin D3 ratio, two metabolites of vitamin D confirmed the enzyme deficiency in vivo. Our observation suggests that this disease could correspond to a rare cause of CPDD.Conclusion: In cases of CPDD associated with calcium values within the upper limit of normal range (or hypercalcemia) with an abnormally low PTH, one could suggest searching for HVD. [ABSTRACT FROM AUTHOR]

A number of medications promote the development of calcium pyrophosphate deposition disease (CPDD). We report 2 cases of acute CPDD after intravenous zoledronic acid therapy. Case #1: a 63-year-old female was admitted for vertebroplasty at the site of an osteoporotic fracture. She received an intravenous infusion of zoledronic acid 5mg on the day after the procedure. Acute CPDD developed in her right knee 24hours later. Findings from joint aspiration and standard radiography confirmed the diagnosis. Case #2: this 79-year-old woman had a history of CPDD was on glucocorticoid and hydroxychloroquine therapy for lupus. She was given an intravenous infusion of zoledronic acid 5mg as prophylaxis of glucocorticoid-induced osteoporosis. Joint pain and a fever developed later on the same day. After 5 days, she had arthritis of the right wrist, laboratory evidence of systemic inflammation, and hypocalcemia. Radiographs showed evidence of CPDD. A Medline search identified 6 cases of bisphosphonate-related CPDD, including 2 due to pamidronate, 2 to etidronate, 1 to alendronic acid, and 1 to neridronic acid. The features were similar to those in our patients, with a short time to onset, systemic inflammation in many cases, a tendency toward hypocalcemia, and radiographs that often showed evidence of CPDD. Bisphosphonate-induced CPDD is a rare eventuality that should nevertheless be borne in mind by rheumatologists. Also, in patients with CPDD while taking bisphosphonate therapy, a role for the drug in the symptoms should be considered. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The main aim of this study was to investigate the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid (SF) obtained from patients with previously diagnosed joint diseases. Methods: We reviewed the results of SF analysis of 5020 samples identifying those collected from patients with a previously definite diagnosis (2370 samples). SF analysis results, age, sex, diagnosis and disease duration were recorded from computerized records of patients’ archives. Results: The prevalence of CPP crystals in SF was 22.28% in osteoarthritis (OA), 8.28% in rheumatoid arthritis (RA), 3.82% in psoriatic arthritis (PsA), 2.79% in other spondyloarthropathies (SpA), 10% in septic arthritis (SeA), 0.66% in gout and 9.18% in the miscellanea of joint diseases, respectively. The prevalence of MSU crystals in SF was 0.30% in RA, 3.34% in PsA, 0.70% in other SpA, 0.80% in acute CPP crystal arthritis (CPP-CA), 0% in OA, reactive arthritis (ReA), SeA, juvenile idiopathic arthritis (JIA) and miscellanea. In OA group, we observed that age and SF inflammatory indices were higher in SF positive to CPP crystals with respect to those without crystals (P <0.0001). In RA, we found that the group of patients with CPP crystals was significantly older (P =0.001) and had a SF less inflammatory (P =0.022) with respect to that without crystals but with a higher disease duration than those without crystals. Conclusion: Crystals can be detected more frequently than expected in SF from joint diseases with a previous established diagnosis. This highlights the importance of SF analysis for the diagnosis of possible comorbidities linked to the presence of crystals. [Copyright &y& Elsevier]

Abstract: Ultrasonography can visualize calcific deposits within soft tissues. The appearance and location of the deposits distinguishes articular chondrocalcinosis from other crystal deposition diseases. The most common findings are hyperechoic dots or lines running parallel to the joint surface, hyperechoic images within fibrous cartilage (menisci and triangular fibrocartilage complex), and deposits within tendons (Achilles tendon). Studies found that ultrasonography was highly sensitive and specific for detecting calcifications, using calcium pyrophosphate dihydrate crystal detection in joint fluid as the reference standard. Good agreement has been demonstrated between radiographs and ultrasonography for the detection of calcifications. Thus, ultrasonography is valuable for diagnosing articular chondrocalcinosis via the detection of calcifications within the joint cartilage, fibrocartilage, and tendons. In addition, ultrasonography is a noninvasive, widely available, inexpensive investigation that requires no radiation exposure. [Copyright &y& Elsevier]

Introduction: Familial calcium pyrophosphate dihydrate deposition disease (CPDD) is uncommon, with about 50 affected families identified to date in the world. Genetic studies in familial CPDD are focusing on the ANKH gene. We report a new Tunisian kindred with CPDD.Patients and Methods: The development of CPDD in a patient who was only 35 years of age prompted a family study. A medical history, physical examination, and radiographs were performed in 103 family members older than 18 years.Results: Fifteen family members had CPDD. There were 10 men and five women, with a mean age of 59.4 years. Onset was usually in the third or fourth decade. Four clinical patterns were found: Five patients had pseudogout, five had pseudoosteoarthritis, three had asymptomatic disease, and two had pseudorheumatoid arthritis. Inheritance was autosomal dominant with low penetrance. No associations with specific HLA antigens were found. The disease was mild. These characteristics fit the description of Gaucher type 1 familial CPDD.Conclusion: Inherited autosomal dominant CPDD with low penetrance was found in 15 members of a Tunisian kindred. The disease was mild. We are planning a genetic study including tests for ANKH gene mutations in this kindred. [ABSTRACT FROM AUTHOR]

Familial calcium pyrophosphate dihydrate deposition (CPPD) disease is a chronic condition in which CPPD microcrystals deposit in the joint fluid, cartilage, and periarticular tissues. Two forms of familial CPPD disease have been identified: CCAL1 and CCAL2. The CCAL1 locus is located on the long arm of chromosome 8 and is associated with CPPD and severe osteoarthritis. The CCAL2 locus has been mapped to the short arm of chromosome 5 and identified in families from the Alsace region of France and the United Kingdom. The ANKH protein is involved in pyrophosphate metabolism and, more specifically, in pyrophosphate transport from the intracellular to the extracellular compartment. Numerous ANKH gene mutations cause familial CCAL2; they enhance ANKH protein activity, thereby elevating extracellular pyrophosphate levels and promoting the formation of pyrophosphate crystals, which produce the manifestations of the disease. Recent studies show that growth factors and cytokines can modify the expression of the normal ANKH protein. These results suggest a role for ANKH in sporadic CPPD disease and in CPPD associated with degenerative disease. [Copyright &y& Elsevier]

Chondrocalcinosis is a common disease occasionally associated with hypercalcemia in case of primary hyperparathyroidism. Familial Hypocalciuric Hypercalcemia (FHH) is a rare and almost always asymptomatic condition, due to an autosomal dominant mutation of the calcium-sensing receptor gene. We report the case of a 61-year-old female with chronic hypercalcemia and joint pain. Clinical and biological data revealed chondrocalcinosis associated with FHH. Since primary hyperparathyroidism may mimic FHH, calcium to creatinine clearance ratio should be calculated in every case to avoid a wrong diagnosis and useless parathyroid surgery. The paucity of FFH complications, including chondrocalcinosis, makes their study difficult: additional studies are needed to clearly evaluate the link between FHH and chondrocalcinosis. [ABSTRACT FROM AUTHOR]

Abstract: Spondylodiscitis are frequent and clinical challenge for practionners. Axial calcium pyrophosphate dihydrate deposition disease (CPDD) is well known for cervical spine involvement with the crowned dens syndrome but other localisations are probably underdiagnosed in sterile spondylodiscitis. We report a case of recurrent sterile spondylodiscitis with epidural abscess related to CPDD proved by vertebral percutaneous needle biopsy with rapid favourable course under colchicine therapy. Axial CPDD could mimic septic spondylodiscitis with epidural abscess on MRI. Sterile spondylodiscitis are probably underdiagnosed forms of microcrystalline disease. Investigations of the presence of microcrystals should be systematically undertaken with tamponed formalin fixed biopsies. If axial CPDD is suspected, colchicine therapy could be a good therapeutic test and would avoid unnecessary antibiotic treatment. [Copyright &y& Elsevier]

Calcium pyrophosphate dihydrate (CPPD) crystals have been shown to trigger the release of IL-1ß, through the activation of an intracellular molecular cascade involving the NLRP3-inflammasome [1]. We have performed an investigator-initiated, double-blind, randomized placebo-controlled trial which evaluated the efficacy and safety of a three-day course of anakinra versus prednisone to treat acute CPPD arthritis. [Extracted from the article]

Abstract: Acute synovitis induced by deposition of calcium pyrophosphate (CPP) and monosodium urate crystals involves interleukin-1β production and activation. The efficacy of blocking interleukin-1β activity (with an interleukin-1 receptor antagonist [anakinra] or interleukin-1β antibody) is well documented for gout attacks but has only been reported in two single-case reports of CPP crystal-induced acute arthritis. Here we report on five cases (four males, mean age 71±27) of CPP crystal-induced inflammatory arthritis refractory and/or intolerant to usual drug therapy and efficiently treated with anakinra. Diagnosis of CPP crystal-induced arthritis was confirmed by identification of crystals in synovial fluid. CPP crystal-induced oligo-arthritis (n =4) and polyarthritis (n =1) were refractory to conventional treatments, including non-steroidal anti-inflammatory drugs, colchicine and steroids (systemic administration or intra-articular injection). After latent infection was ruled out, anakinra, 100mg/day, was administered subcutaneously for 3 days. Four patients showed rapid clinical and biological responses at a mean of 3 days after treatment. Anakinra provided good joint pain relief (baseline 0–100mm visual analog scale score 60±17mm, outcome 10±10mm) and decreased serum C-reactive protein level (58±43 to 5±2mg/L). Anakinra was well tolerated. One injection-site skin reaction was observed but no infection. Anakinra was effective and safe in this small series of patients with refractory arthritis due to acute CPP crystal deposition. [Copyright &y& Elsevier]

Abstract: Background: Calcium pyrophosphate dihydrate crystal deposition disease (CPPD-CDD) has been associated to hypercalcemia. Familial hypocalciuric hypercalcemia (FHH) is a rare but important consideration in the differential diagnosis of hypercalcemia. This autosomal dominantly inherited condition is characterized by elevated plasma calcium levels, relative or absolute hypocalciuria, and normal to moderately elevated plasma PTH level. The disease is caused by inactivating mutations in the calcium-sensing receptor gene. Case report: We describe a 77-year-old Italian man with arthritis secondary to CPPD-CDD and hypercalcemia. Clinical and biochemical data (s-Ca: 2.94mmol/L; PTH: 5.9 pmol/L; 24 h urinary calcium: 69.6mg; calcium/creatinine clearance: 0.004) suggested the diagnosis of FHH. Mild hypocalciuric hypercalcemia was also found in five of seven relatives confirming the diagnosis, of these one showed chondrocalcinosis. Conclusions: It is important to screen for FHH using fractional urinary excretion of calcium in subjects with CPPD-CDD associated to hypercalcemia, this approach may prevent unnecessary parathyroidectomy. [Copyright &y& Elsevier]

Abstract: We describe the case of a 71-year-old man with recurrent pseudogout attacks affecting multiple joints. He had end-stage renal failure that contra-indicated the use of non-steroidal anti-inflammatory drugs and was resistant to therapy with glucocorticoids. Based on the recent findings that interleukin (IL)-1β is involved in crystal-induced inflammation, the patient received anakinra, a specific IL-1 inhibitor, in order to treat an acute attack of pseudogout. In addition, anakinra was administered as preventive therapy 3days per week after each hemodialysis session. Under this treatment, he did not present any severe episode of arthritis after a follow-up of 8months. This observation suggests that anakinra is efficacious and safe for the prevention of crystal-induced arthritis in patients with severe renal failure. [Copyright &y& Elsevier]