Crystal Deposition In Patients Research Articles

CPPD and Associated Crystals in Clinically Diagnosed Chondrocalcinosis: A Clinicopathological Study of 20 Patients

Introduction: Chondrocalcinosis (Ch-C), induced by calcium pyrophosphate dihydrate crystals (CPPD) [Ca2P2O7.2H2O] is considered as a distinct metabolic disease and a well-defined clinical entity, with characteristic clinical manifestations and symptoms. This study used previously found method by the author .i.e, non-staining approach to discover crystal deposits in patients with clinically diagnosed Ch-C, to find a possible correlation between coexisting crystals, and to assess the role of coexistent crystals in inflammatory cellular processes of joints. Patients and methods: There were forty (40) surgical specimens that had been traditionally processed from 16 patients who had been clinically diagnosed with Ch-C. Results: In unstained tissue sections CPPD crystals were found in 22 of 40 samples of all 16 patients. Beside the CPPD crystals calcium hydroxyapatite (HA) [Ca5(PO4)3(OH)] crystals were found in 26 tissue samples of all 16 patients, cholesterol (CC) [C27H46O] in 23 tissue samples of 12 patients, and crystalline liquid lipid droplets (CL) in 11 tissue samples of 5 patients. More or less amorphous deposits of calcium carbonate [CaCO3] and/or calcium phosphate [Ca3(PO4)2] were present alongside CPPD and the contemporaneous crystals. There was a significant and positive correlation between prevalence of CPPD and HA. The connection between inflammatory cellular infiltration and CPPD, HA, CC or CL crystals surrounded by mineral deposits was not significant. Conclusions: The non-staining approach is a practical, low-tech way to find CPPD, HA, CC, and other crystals (with or without CL). The positive and significant correlation between CPPD and HA support the earlier premise that CPPD and HA represent basically an identical metabolic disorder). CPPD and/or HA crystals can provoke inflammatory processes responsible for the clinical symptoms, but the variable amounts of amorphous minerals enclose (isolate) the crystals, and can reduce or eliminate the inflammatory reaction. The authors assume that CC (with or without CL) is an associated phenomenon (concomitant fat metabolic malady) without direct cause of inflammation, and is not responsible for clinical symptoms of crystal induced arthropathies.

Development and validation of an OMERACT ultrasound scoring system for the extent of calcium pyrophosphate crystal deposition at the joint level and patient level.

The Calcium Pyrophosphate Deposition (CPPD) subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound working group was established to validate ultrasound as an outcome measure instrument for CPPD, and in 2017 has developed and validated standardised definitions for elementary lesions for the detection of calcium pyrophosphate crystals in joints. The aim of this study was to develop and evaluate the reliability of a consensus-based ultrasound scoring system for CPPD extent, representing the next phase in the OMERACT methodology. In this study the novel scoring system for CPPD was developed through a stepwise process, following an established OMERACT ultrasound methodology. Following a previous systematic review to gather available evidence on existing scoring systems for CPPD, the novel scoring system was developed through a Delphi survey based on the expert opinion of the members of the OMERACT Ultrasound working group-CPPD subgroup. The reliability of the scoring system was then tested on a web-based and patient-based exercise. Intra-reader and inter-reader reliability of the new scoring system was assessed using weighted Light's κ coefficients. The four-grade semiquantitative scoring system consisted of: grade 0 (no findings consistent with CPPD), grade 1 (≤3 single spots or 1 small deposit), grade 2 (>3 single spots or >1 small deposit or ≥1 larger deposit occupying ≤50% of the structure under examination in the reference image-ie, the scanning view with the highest grade of depositions), and grade 3 (deposits that occupy more than 50% of the structure under examination in the reference image). The score should be applied to the knee (menisci and hyaline cartilage) and the triangular fibrocartilage complex of the wrist. The intra-reader and inter-reader reliabilities on static images were almost perfect (κ 0·90 [95% CI 0·79-1·00] and κ 0·84 [0·79-0·88]), and on the eight patients recruited (four [50%] female and four [50%] male) were substantial (κ 0·72 [95% CI 0·47 to 0·96] and 0·66 [0·61 to 0·71]). This OMERACT ultrasound scoring system for CPPD was reliable on both static images and patients. The scoring system might be a valuable tool for ensuring valid and comparable results in clinical trials and could help monitor the extent of crystal deposition in patients with CPPD in clinical practice. The Italian Ministry of Health - Ricerca Corrente.

Sonography as method for diagnosing gout at preclinical stage (preliminary data from pilot study)

Gout is one of the most common rheumatic diseases, the peculiarity of which is the development in conditions of prolonged hyperuricemia (HU). The rapid increase in the incidence of gout with a slight increase in the prevalence of HU actualizes the issue of diagnosing gout at the preclinical stage.Objective. To determine the frequency of ultrasound signs of urate crystal deposition in patients with asymptomatic HU (AHU) and gout.Results. 112 patients with AHU and gout were included, the mean age in both groups was 49.7 years. Ultrasound signs of deposition of sodium monourate crystals (SMC) among patients with AHU were determined in 21.1% of the patient by ultrasound of the knee joints and 17.5% of patients by ultrasound of the feet. Patients with gout showed the same US features in 38.1% and 56.3% of cases, respectively. There is a strong correlation between the detection of SMC by ultrasound and a history of arthritis attack of the respective joints.Conclusions. The detection of SMC and concomitant HU is very common among patients with AHU, which can be considered the preclinical stage of gout.

OP0168 DEVELOPMENT OF AN ULTRASOUND SCORING SYSTEM FOR CPPD EXTENT: RESULTS FROM A DELPHI PROCESS AND WEB-RELIABILITY EXERCISE BY THE OMERACT US WORKING GROUP

BackgroundUltrasound (US) has proven to be an excellent imaging technique for detecting calcium pyrophosphate (CPP) deposition disease (CPPD); it is also widely available and inexpensive and can be performed during the clinic visit making it the preferred imaging modality for many rheumatologists. However, no validated grading systems have yet been developed allowing for a quantification of the extent of crystal deposition in CPPD.ObjectivesThe aim of this study was to develop a scoring system for the quantification of CPP deposition at a patient level according to the OMERACT framework.MethodsAs part of the OMERACT methodology, we performed a systematic literature review (SLR) and meta-analysis aimed to estimate the prevalence of CPP deposition in peripheral joints by imaging, in order to identify relevant joints for CPPD monitoring. A preliminary survey was also circulated among the members of the OMERACT US – CPPD working group to collect their own suggestions according to their personal experience. Subsequently, a Delphi survey was prepared and circulated between members of the group, including statements that reflected both the results of the SLR and of the preliminary survey. In total, 32 statements were generated regarding the type of scoring for single structures, the sites to be included, the final scoring at patient level, and the scanning technique. Participants were asked to reply on a 5-point Likert scale (1, strongly disagree to 5, strongly agree) and agreement was achieved when 4 and 5 grades reached 75% or more of concordance. In case of disagreement, new statements were proposed according to the members’ suggestions and circulated for voting in a subsequent round. After agreement of a scoring system, the validation process began. Two rounds of a web-based exercise on static images were conducted on 120 images representing equally all sites under investigation and all degrees of crystal deposition, to assess the intra- and inter-reader reliability of the new scoring system. Representative images of the scoring system were visible throughout the entire exercise in order to facilitate the scoring of the lesions.ResultsThree Delphi rounds were needed to reach agreement on all items. 32/41 members of the OMERACT US-CPPD working group replied in the first round, 26/32 in the second, and 25/26 in the third round. Twenty statements were approved in the first round, 3 in the second, and 3 in the third round. Only the knees (menisci and hyaline cartilage) and the triangular fibrocartilage of the wrist were included in the final score, using a four-grade system (0-3). It was decided that each anatomical structure should be scored separately and then also summed in order to define the joint score. The sum of the assessed joints was the total score at patient level. The final scoring system with the definitions and the relative technical notes is represented in Figure 1. 33/41 members participated to the reliability exercise. The inter-reader reliability of the scoring was substantial (kappa of 0.72), and the intra-reader reliability was almost perfect (kappa of 0.82).ConclusionThis is the first study for developing a scoring system for the extent of CPP crystal deposition in patients with CPPD. The scoring system demonstrated to be reliable in static images. The next step of the validation process is to assess the reliability of the scoring system in a patient-based exercise. This study represents a fundamental step in the OMERACT process of validating US as an outcome measure instrument, and above proposed scoring system will hopefully provide a useful tool for clinical practice and research.Disclosure of InterestsNone declared

Spectral domain optical coherence tomography-based retinochoroidal cystine crystal score: a window into infantile nephropathic cystinosis

PrécisCystinosis is a lysosomal storage disease leading to an accumulation of cystine crystals in several organs. We aim to comprehensively describe chorioretinal cystine crystals via spectral domain optical coherence tomography...

Risk factors and diagnostic value for ultrasound-detected tendon monosodium urate crystal deposition in patients with gout

OBJECTIVE To evaluate frequency and patterns, risk factors of MSU (monosodium urate) crystal deposition at lower extremity tendon by ultrasonography in gout patients, and to explore diagnostic value by ultrasonography. METHODS Patients diagnosed with gout and age matched healthy controls had ultrasound scanning of both feet and knees including joints and tendons (achilles, quadriceps, and patellar tendon). Readers who scored the ultrasound scans for MSU crystal deposition were blinded to the patients' clinical diagnoses. Clinical characteristics were compared between positive and negative crystal deposition groups by US, and risk factors of MSU deposition in tendons were analyzed. Diagnostic values of MSU deposition were evaluated by ultrasonography according with positive MSU crystal in synovial fluid or tophi by polarized microscopy. RESULTS Eighty patients and eighty healthy controls were included. Thity-three patients (47.5%) had tophi by physical examination. The achilles tendon was the most commonly involved tendon site 41(51.2%), followed by the quadriceps tendons 22(27.5%), and patella tendon 10(12.5%). There were no MSU deposition in healthy control group at tendon by ultrasonography. Compared with negative MSU deposition at tendon site by ultrasonography, tendon MSU positive patients had longer mean gout duration [(87.3±40.9) months vs. (7.7±2.6) months, P=0.001];higher frequency of gout flare [2(1, 2) /year vs. 1(1, 1) /year, P=0.001]; higher BMI [(26.3±2.5) kg/m2vs. (23.3±2.1) kg/m2, P=0.05]. Also, the mean serum uric acid and creatinine levels were higher in tendon MSU positive group [(584.6±87.6) μmol/L vs. (460.4±96.7) μmol/L, P=0.001] and [(90.9±33.3) μmol/L vs. (70.6±40.2) μmol/L, P=0.02] separately. Logistic regression analysis showed gout duration and flare frequency were independent risk factors for MSU deposition at tendon by ultrasonography (P < 0.01). Joint or tophi aspirations were performed in all the eighty gout patients, and positive MSU crystals in synovial fluid analysis by polarized microscopy were defined as the golden standard of gout diagnosis. When compared with the golden standard, the sensitivity and specificity were 94.0% and 78.0% separately for MSU deposition at tendon by ultrasonography. CONCLUSION Tendon involvement at the lower extremity tendons in gout is very common. Long gout disease duration and high frequency of gout flare are both independent risk factors of tendon MSU deposition by ultrasonography. Ultrasonography had good sensitivity and specificity for detecting tendinous tophi and aggregates.

Identification of monosodium urate crystal deposits in patients with asymptomatic hyperuricemia using dual-energy CT

ObjectivesDual-energy CT (DECT) scan is a sensitive and specific tool used to visualise and quantify monosodium urate (MSU) crystal deposits in the joints. Few studies have examined MSU crystal deposits...

Cysteamine hydrochloride eye drop solution for the treatment of corneal cystine crystal deposits in patients with cystinosis: an evidence-based review.

Cystinosis is a rare, autosomal recessive disorder leading to defective transport of cystine out of lysosomes. Subsequent cystine crystal accumulation can occur in various tissues, including the ocular surface. This review explores the efficacy of cysteamine hydrochloride eye drops in the treatment of corneal cystine crystal accumulation and its safety profile.

Presence of monosodium urate crystal deposition by dual-energy CT in patients with gout treated with allopurinol

ObjectiveDual-energy CT (DECT) detects and quantifies monosodium urate (MSU) crystal deposition with high precision. This DECT study assessed crystal deposition in patients with gout treated with stable-dose allopurinol, and investigated...

Erratum to: Cystadrops® (cysteamine hydrochloride 0.55% viscous eye-drops solution) in treating corneal cystine crystal deposits in patients with cystinosis: a profile of its use

Erratum to: Cystadrops® (cysteamine hydrochloride 0.55% viscous eye-drops solution) in treating corneal cystine crystal deposits in patients with cystinosis: a profile of its use

Cystadrops® (cysteamine hydrochloride 0.55% viscous eye-drops solution) in treating corneal cystine crystal deposits in patients with cystinosis: a profile of its use

Cystadrops® (viscous cysteamine hydrochloride 0.55% eye-drops solution) is the first orphan drug approved in the EU for the treatment of corneal crystal deposits in adults and children aged >2 years with cystinosis. The solution reduced the accumulation of cystine crystals in the cornea and the severity of photophobia in patients of all ages with cystinosis in clinical studies. Instillation adverse effects (e.g. burning and stinging) may occur, but generally are very transient and mild to moderate in severity. Relative to extemporaneously prepared formulations of cysteamine hydrochloride eye drops, Cystadrops® requires less frequent administration (relieving treatment burden), displays better stability (making storage, distribution and use by patients less difficult) and provides reliable standardization and availability.

Efficacy of topical cysteamine in nephropathic cystinosis

PurposeThe aim of this study is to evaluate the efficacy of topical cysteamine 0.55% eye drops in the treatment of corneal cystine crystal deposits in patients with nephropathic cystinosis.MethodsThirty-two patients...

Relevant aspects of imaging in the diagnosis and management of gout

Gout is an inflammatory arthritis characterized by the deposition of monosodium urate crystals in the synovial membrane, articular cartilage and periarticular tissues leading to inflammation. Men are more commonly affected, mainly after the 5th decade of life. Its incidence has been growing with the population aging.In the majority of the cases, the diagnosis is made by clinical criteria and synovial fluid analysis, in search for monosodium urate crystals. Nonetheless, gout may sometimes have atypical presentations, complicating the diagnosis. In these situations, imaging methods have a fundamental role, aiding in the diagnostic confirmation or excluding other possible differential diagnosis.Conventional radiographs are still the most commonly used method in gout patients’ evaluation; nevertheless, this is not a sensitive method, since it detect only late alterations.In the last years, there have been several advances in imaging methods for gout patients. Ultrasound has shown a great accuracy in the diagnosis of gout, identifying monosodium urate deposits in the synovial membrane and articular cartilage, in detecting and characterizing tophi and in identifying tophaceous tendinopathy and enthesopathy. Ultrasound has also been able to show crystal deposition in patients with articular pain in the absence of a classical gout crisis.Computed tomography is an excellent method for detecting bone erosions, being useful in spine involvement. Dual-energy CT is a new method able to provide information about the chemical composition of tissues, with high accuracy in the identification of monosodium urate deposits, even in the early stages of the disease and in cases of difficult characterization.Magnetic resonance imaging is useful in the evaluation of deep tissues not accessible by ultrasound.Besides the diagnosis, with the emergence of new drugs that aim to reduce tophaceous burden, imaging methods have become useful tools in monitoring the treatment of patients with gout.

Silent Monosodium Urate Crystal Deposits Are Associated With Severe Coronary Calcification in Asymptomatic Hyperuricemia: An Exploratory Study.

To evaluate the association between monosodium urate (MSU) crystal deposits in patients with asymptomatic hyperuricemia and the severity and extension of coronary artery disease (CAD). In this cross-sectional study, consecutive inpatients with a non-ST elevation acute coronary event and asymptomatic hyperuricemia (serum uric acid concentration of ≥7.0 mg/dl) or normouricemia (serum uric acid concentration of <7.0 mg/dl) were enrolled. In patients with asymptomatic hyperuricemia, the presence of MSU crystals was determined by ultrasound evaluation of both knees and first metatarsophalangeal joints and by compensated polarized light microscopy. CAD was assessed by coronary angiography, and the following variables were considered: 1) the presence of moderate-to-severe coronary artery calcification, 2) the number of significant coronary stenoses, and 3) the presence of multivessel disease. The association between variables indicating the severity of CAD and the presence of MSU crystals was analyzed by multivariate regression. One hundred forty patients were enrolled. After ultrasonography and microscopic analyses were performed, the patients were classified as having normouricemia (n = 66), asymptomatic hyperuricemia alone (n = 61), and asymptomatic hyperuricemia with MSU crystals (n = 13). The prevalence of moderate-to-severe coronary calcification was significantly higher in the patients with asymptomatic hyperuricemia with MSU crystals compared with patients with asymptomatic hyperuricemia alone and patients with normouricemia (P = 0.003). An independent association was observed between the presence of moderate-to-severe calcification and asymptomatic hyperuricemia with crystals (odds ratio 16.8, P = 0.002). No significant association was observed for the other variables. Silent deposition of MSU crystals in patients with asymptomatic hyperuricemia was associated with more severe coronary calcification, which suggests more severe CAD in relation to crystal deposition.

Aspectos relevantes do diagnóstico e seguimento por imagem na gota

Gout is an inflammatory arthritis characterized by the deposition of monosodium urate crystals (MSU) in the synovial membrane, articular cartilage and periarticular tissues leading to inflammation. Men are more commonly affected, mainly after the 5th decade of life. Its incidence has been growing with the population ageing.In the majority of the cases, the diagnosis is made by clinical criteria and synovial fluid analysis, in search for MSU crystals. Nonetheless, gout may sometimes have atypical presentations, complicating the diagnosis. In these situations, imaging methods have a fundamental role, aiding in the diagnostic confirmation or excluding other possible differential diagnosis.Conventional radiographs are still the most commonly used method in gout patients’ evaluation; nevertheless, this is not a sensitive method, since it detect only late alterations.In the last years, there have been several advances in imaging methods for gout patients. Ultrasound has shown a great accuracy in the diagnosis of gout, identifying MSU deposits in the synovial membrane and articular cartilage, in detecting and characterizing tophi and in identifying tophaceous tendinopathy and enthesopathy. Ultrasound has also been able to show crystal deposition in patients with articular pain in the absence of a classical gout crisis.Computed tomography is an excellent method for detecting bone erosions, being useful in spine involvement. Dual‐energy CT is a new method able to provide information about the chemical composition of tissues, with high accuracy in the identification of MSU deposits, even in the early stages of the disease and in cases of difficult characterization.Magnetic resonance imaging is useful in the evaluation of deep tissues not accessible by ultrasound.Besides the diagnosis, with the emergence of new drugs that aim to reduce tophaceous burden, imaging methods have become useful tools in monitoring the treatment of patients with gout.

Tendon Involvement in Patients with Gout

Dual-energy computed tomography (CT) can be used to identify sites of monosodium urate (MSU) crystal deposition in patients with gout (NEJM JW Gen Med

Tendon involvement in the feet of patients with gout: a dual-energy CT study

ObjectivesTo examine the frequency and patterns of monosodium urate (MSU) crystal deposition in tendons and ligaments in patients with gout using dual-energy CT (DECT).MethodsNinety-two patients with tophaceous gout had DECT...

Calcium Pyrophosphate Crystals Detected by Ultrasound in Patients without Radiographic Evidence of Cartilage Calcifications: Figure 1A-B.

There is a consistent body of evidence supporting the role of ultrasound in patients with rheumatoid arthritis (RA)1,2. More recently, ultrasound is gaining interest among rheumatologists for the assessment of calcium pyrophosphate dihydrate (CPPD) disease3,4,5, because it has demonstrated high specificity in the detection of pathological findings indicative of pyrophosphate crystal deposits6,7,8. The definite diagnosis of CPPD disease requires identification of CPPD crystals in the synovial fluid by polarizing light microscopy. However, aspiration of the synovial fluid is not always possible for many reasons. In those cases, imaging modalities are important as surrogate diagnostic tools. We describe 2 cases showing the diagnostic potential of ultrasound in the detection of pyrophosphate crystal deposits in patients with negative radiographic evidence of cartilage calcifications. A 58-year-old woman presented to our clinic for a history of recurrent attacks of monoarthritis at right knee level, associated …

Renal histopathology and crystal deposits in patients with small bowel resection and calcium oxalate stone disease

We present here the anatomy and histopathology of kidneys from 11 patients with renal stones following small bowel resection, including 10 with Crohn's disease and 1 resection in infancy for unknown cause. They presented predominantly with calcium oxalate stones. Risks of formation included hyperoxaluria (urine oxalate excretion greater than 45 mg per day) in half of the cases, and acidic urine of reduced volume. As was found with ileostomy and obesity bypass, inner medullary collecting ducts (IMCDs) contained crystal deposits associated with cell injury, interstitial inflammation, and papillary deformity. Cortical changes included modest glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Randall's plaque (interstitial papillary apatite) was abundant, with calcium oxalate stone overgrowth similar to that seen in ileostomy, idiopathic calcium oxalate stone formers, and primary hyperparathyroidism. Abundant plaque was compatible with the low urine volume and pH. The IMCD deposits all contained apatite, with calcium oxalate present in three cases, similar to findings in patients with obesity bypass but not an ileostomy. The mechanisms for calcium oxalate stone formation in IMCDs include elevated urine and presumably tubule fluid calcium oxalate supersaturation, but a low calcium to oxalate ratio. However, the mechanisms for the presence of IMCD apatite remain unknown.

In Vivo Confocal Microscopy and Anterior Segment Optical Coherence Tomography Analysis of the Cornea in Nephropathic Cystinosis

To analyze the corneas of patients with nephropathic cystinosis using in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT). Prospective case series. Sixteen eyes of 8 patients with nephropathic cystinosis aged 8 to 21 years. The ophthalmologic evaluation included best-corrected visual acuity, evaluation of photophobia (0-4), slit-lamp biomicroscopy analysis, intraocular pressure measurement, evaluation of crystal density using a slit-lamp-based scoring of the cornea, as well as AS-OCT and IVCM analysis. The depth of crystal deposition (DCD) in the central cornea and the central cornea thickness (CCT) were assessed using AS-OCT and IVCM. The IVCM images were evaluated for crystal density in each corneal layer and an IVCM score was calculated for each eye. All eyes had corneal crystal deposits, with a mean slit-lamp photography score of 2.90+/-0.13 (range, 2.75-3.00). Using AS-OCT, corneal crystals were observed in all eyes. These crystals appeared as hyperreflective punctuate deposits, predominantly observed within the anterior stroma. Measured with AS-OCT, the mean depth of DCD in the central cornea was 291.40+/-81.42 microm (range, 200-531 microm); the mean CCT was 543.47+/-29.62 microm. Using IVCM, the crystals appeared as spindle, needle-shaped, and fusiform hyperreflective bodies measuring from 1 to 175 microm in length and 1 to 30 microm in thickness. Except for the endothelium, randomly oriented crystals were observed in all corneal layers, with the greatest density observed within the anterior stroma. Measured with IVCM, the mean DCD was 426.07+/-88.19 microm (range, 284-531 microm); the mean CCT was 531.87+/-34.77 microm. There was no significant difference between the CCT measurements obtained with IVCM and with AS-OCT (mean difference, 11.31 microm; P = 0.07). Nevertheless, the DCD was significantly higher with IVCM than with AS-OCT (mean difference, 126.25 microm; P<0.0001). In patients with nephropathic cystinosis, IVCM could precisely quantify the density of crystals within the central cornea. Anterior segment OCT and IVCM should be used in further studies evaluating crystal deposition in patients with nephropathic cystinosis. The authors have no proprietary or commercial interest in any materials discussed in this article.