[First classification criteria for diseases caused by calcium pyrophosphate deposition (CPPD)-Translation, explanation and assessment]. / Erste Klassifikationskriterien für durch Kalziumpyrophosphatablagerungen verursachte Erkrankungen ­ Übersetzung, Erläuterung und Bewertung.

AIM: For diseases caused by calcium pyrophosphate deposition (CPPD), validated classification criteria were previously lacking. In this article the recently developed and validated classification criteria are translated, explained, and assessed. METHODS: In recent years a multinational research group developed classification criteria for CPPD disease with the support by the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR), following an established method. The developed criteria were finally validated in an independent cohort. The translation and annotation of the new first classification criteria were carried out in an iterative procedure in consensus with the authors. RESULTS: The presence of a crowned dens syndrome or calcium pyrophosphate crystals in the synovial fluid in patients with pain, swelling or sensitivity of the joints (entry criterion) is sufficient for the classification as CPPD disease, where the symptoms cannot be completely explained by another rheumatic disease (exclusion criterion). If these symptoms are not present, a count of more than 56 points based on weighted criteria comprised of clinical features and the results of laboratory and imaging investigations can be included for classification as a CPPD disease. These criteria had a sensitivity of 92.2% and a specificity of 87.9% in the derivation cohorts (190 CPPD cases and 148 mimics), whereas the sensitivity was 99.2% and the specificity 92.5% in the validation cohorts (251 CPPD cases and 162 mimics). CONCLUSION: The ACR/EULAR classification criteria 2023 of a CPPD disease will facilitate clinical research in this field. The use in the clinical routine will show how practical the criteria are.

Issues in CPPD Nomenclature and Classification.

PURPOSE OF REVIEW: This paper covers confusion and challenges in the nomenclature of calcium pyrophosphate deposition disease. Clinicians, investigators, and patients are faced with a variety of terms that are used to describe CPPD and its phenotypes, and clarity is greatly needed to help advance research and patient care. Motivation for the upcoming development of CPPD classification criteria is reviewed. RECENT FINDINGS: EULAR proposed recommended terminology for CPPD in 2011. International Classification of Diseases (ICD-9 and ICD-10) billing codes identify definite or probable CPPD with variable accuracy depending on the clinical setting and comparator group. READ diagnostic codes have been employed to identify pseudogout in UK datasets but their accuracy has not been evaluated. CPPD classification criteria will provide a system for identifying a relatively homogenous group of patients to be included in clinical studies, enabling comparison of outcomes across studies. CPPD nomenclature remains challenging for clinicians, investigators, and patients. A lay-friendly definition of CPPD, using easily accessible terminology, would be welcome. CPPD classification criteria are a necessary step in moving forward CPPD clinical research and may involve a range of clinical, laboratory, and imaging modalities.

Pseudogout among Patients Fulfilling a Billing Code Algorithm for Calcium Pyrophosphate Deposition Disease.

To test the performance of a billing claims-based calcium pyrophosphate deposition disease (CPPD) algorithm for identifying pseudogout. We applied a published CPPD algorithm at an academic institution and randomly selected 100 patients for electronic medical record review for 3 phenotypes: (1) definite/probable CPPD, (2) definite/probable pseudogout; (3) definite pseudogout. Clinical data were recorded and positive predictive value (PPV) (95% CI) for each phenotype was calculated. We then modified the published algorithm to require ≥ 1 of 4 relevant terms ("pseudogout", "calcium pyrophosphate crystals", "CPPD", or "chondrocalcinosis") through automated text searching in clinical notes, and re-calculated PPVs. To estimate the percentage of pseudogout patients not identified by the published algorithm, we reviewed a random sample of 50 patients with ≥ 1 of 4 relevant terms in clinical notes who did not fulfill the published algorithm. Among patients fulfilling the published algorithm, 68% had ≥ 1 of 3 phenotypes. The published algorithm had PPV 24.0% (95% CI 19.3-28.7%) for definite/probable pseudogout and 18.0% (95% CI 14.5-21.5%) for definite pseudogout. Requiring ≥ 1 of 4 relevant terms in clinical notes increased PPV to 33.3% (95% CI 26.8-39.8%) for definite/probable pseudogout and 24.6% (95% CI 19.8-29.4%) for definite pseudogout. Among patients not fulfilling the published algorithm, 16.0% had definite/probable pseudogout and 6.0% had definite pseudogout. A billing code-based CPPD algorithm had low PPV for identifying pseudogout. Adding text searching modestly enhanced the PPV, though it remained low. These findings highlight the need for improved approaches to identify pseudogout to facilitate epidemiologic studies.

Validation of administrative codes for calcium pyrophosphate deposition: a Veterans Administration study.

BACKGROUND: Despite high prevalence, progress in calcium pyrophosphate deposition (CPPD) has been limited by poor awareness and absence of validated approaches to study it in large data sets. OBJECTIVES: We aimed to determine the accuracy of administrative codes for the diagnosis of CPPD as a foundational step for future studies. METHODS: We identified all patients with an International Classification of Diseases, Ninth Revision, Clinical Modification code for chondrocalcinosis (712.1-712.39) or pseudogout/other disorders of mineral metabolism (275.49), and convenience sample selected a comparison group with gout (274.00-03 or 274.8-9), or rheumatoid arthritis (714.0) from 2009 to 2011 at a Veterans Affairs medical center. Each patient was categorized as having definite, probable, or possible CPPD or absence of CPPD based on the McCarty and Ryan criteria using chart abstracted data including crystal analysis, radiographs, and arthritis history. RESULTS: Two hundred forty-nine patients met the clinical gold standard criteria for CPPD based on medical records, whereas 48 patients met definite criteria, 183 probable, and 18 met possible criteria. The accuracy of administrative claims with a code of 712 or 275.49 for definite or probable CPPD was as follows: 98% sensitivity (95% confidence interval, 96%-99%), 78% specificity (74%-83%), 91% positive predictive value, and 94% negative predictive value. CONCLUSIONS: At this center, single administrative code 275.49 or 712 accurately identifies patients with CPPD with a positive predictive value of 91%. These findings suggest that administrative codes can have strong clinical accuracy and merit further validation to allow adoption in future epidemiologic studies of CPPD.

Role of Newman's classification in predicting outcomes in patients with crystal arthritis.

PURPOSE: The aim of the study was to evaluate the utility of Newman's classification in predicting outcomes in patients presenting with crystal arthritis. METHODS: Between January and December 2009, all patients who presented to our institution with acute crystal arthritis and were investigated with microbiological assessment of their synovial fluid were included in the study. Patients were divided into two groups depending on the fulfilment of Newman's criteria for culture-negative septic arthritis. Group 1 included patients that fulfilled Newman's B criteria. Group 2 included patients that fulfilled Newman's C criteria. A database looking at the demographics, mode of presentation, investigations, treatment and outcomes was then established and the results compared between the two groups. RESULTS: A total of 58 patients were identified (group 1: n = 13; group 2: n = 45). The average age was 71 years (range 33-96). The joint most commonly involved was the knee followed by the wrist. Clinical findings at presentation were comparable in both groups; however, WBC and C-reactive protein (CRP) were more likely to be raised in group 1. Although most patients in group 1 were treated with antibiotics (62%) there was still a higher rate of morbidity, greater use of supportive therapy and a longer hospital stay (22.3 days, SD 17.4) in comparison with group 2, where most patients were treated by observation only (76%, mean hospital stay 3.5 days, SD ± 4.4). The difference in length of hospital stay was statistically significant (p < 0.0001). CONCLUSIONS: Newman's criteria are a good indicator for prognosis in patients with crystal arthritis. However, the presence of crystals in an acutely inflamed joint does not exclude the need for supportive therapy and long hospital stay even in the absence of positive synovial fluid culture.

Classifying Pseudogout Using Machine Learning Approaches With Electronic Health Record Data.

OBJECTIVE: Identifying pseudogout in large data sets is difficult due to its episodic nature and a lack of billing codes specific to this acute subtype of calcium pyrophosphate (CPP) deposition disease. The objective of this study was to evaluate a novel machine learning approach for classifying pseudogout using electronic health record (EHR) data. METHODS: We created an EHR data mart of patients with ≥1 relevant billing code or ≥2 natural language processing (NLP) mentions of pseudogout or chondrocalcinosis, 1991-2017. We selected 900 subjects for gold standard chart review for definite pseudogout (synovitis + synovial fluid CPP crystals), probable pseudogout (synovitis + chondrocalcinosis), or not pseudogout. We applied a topic modeling approach to identify definite/probable pseudogout. A combined algorithm included topic modeling plus manually reviewed CPP crystal results. We compared algorithm performance and cohorts identified by billing codes, the presence of CPP crystals, topic modeling, and a combined algorithm. RESULTS: Among 900 subjects, 123 (13.7%) had pseudogout by chart review (68 definite, 55 probable). Billing codes had a sensitivity of 65% and a positive predictive value (PPV) of 22% for pseudogout. The presence of CPP crystals had a sensitivity of 29% and a PPV of 92%. Without using CPP crystal results, topic modeling had a sensitivity of 29% and a PPV of 79%. The combined algorithm yielded a sensitivity of 42% and a PPV of 81%. The combined algorithm identified 50% more patients than the presence of CPP crystals; the latter captured a portion of definite pseudogout and missed probable pseudogout. CONCLUSION: For pseudogout, an episodic disease with no specific billing code, combining NLP, machine learning methods, and synovial fluid laboratory results yielded an algorithm that significantly boosted the PPV compared to billing codes.

[Chondrocalcinosis and calcium pyrophosphate (CPP) crystal deposition disease in 2010]. / Chondrocalcinose et arthropathies a dépôts de cristaux de pyrophosphate de calcium: actualité 2010.

Chondrocalcinosis may be asymptomatic or take three classical forms (acute recurrent inflammatory, chronic inflammatory, with osteoarthritis). Apart form that, CPP crystal arthropathies can mimic several rheumatic diseases, including polymyalgia, septic arthritis and spondylodiscitis. Several conditions can predispose to chondrocalcinosis, including hemochromatosis, hyperparathyroidism, familial hypocalciuric hypercalcemia, hypomagnesemia and treatment with tacrolimus or diuretics. The diagnostic sensitivity of ultrasound seems better than radiography and CT is useful in spinal forms but whenever possible, the identification of crystals in synovial fluid remains essential. NSAIDs and/or glucocorticoids are frequently sufficient to control symptoms but methotrexate, at anti-inflammatory doses (10-20 mg/wk) appears useful in refractory forms.

Clinical aspects of calcium pyrophosphate dihydrate crystal deposition.

CPPD deposition occurs in a wide variety of clinical settings, most commonly as an age-related phenomenon in the absence of other joint abnormality. Although our knowledge of CPPD and other intra-articular particles has increased in the last decade, the role of CPPD remains unclear. The paradox of asymptomatic deposition of phlogistic crystals, the wide spectrum of clinical presentation, and the lack of disease specificity, however, have challenged recognition of pyrophosphate arthropathy (PA) as a separate, distinct disease entity and led to reappraisal of earlier concepts of crystal deposition disease. In this article, clinical aspects of PA will first be presented; the validity of PA as a discrete arthropathy will then be discussed.

Chondrocalcinosis of the wrist.

Calcium Pyrophosphate Dihydrate Deposition (CPDD) disease has characteristic radiographic features including soft tissue calcification, joint space narrowing, bone sclerosis, subchondral cyst formation without osteophyte formation, and large intraosseous geodes. Triangular fibrocartilage calcification is frequently found and isolated scapho-trapezio-trapezoid (STT) arthritis is specific for CPDD. Distal radio-ulnar (DRUJ), isolated midcarpal joint and piso-triquetral joint involvement also occur. 127 patients were reviewed. Seventy-eight had symptomatic STT joint arthritis, for which 36 underwent surgery. Twenty-two patients had a SLAC wrist deformity for which ten underwent surgery. Eight patients had isolated midcarpal arthritis for which three midcarpal arthrodeses, two four-bone arthrodeses and two carpal tunnel releases were performed. Nineteen patients had a generalized arthritis and seven of the patients underwent surgery: four-corner arthrodesis+scaphoidectomy (one case), carpal tunnel release (two cases) extensor synovectomy (two cases) and trigger finger release (two cases).

Performance of hand radiographs in predicting the diagnosis in patients with early arthritis.

OBJECTIVE: To evaluate the ability of baseline hand radiographs to predict the diagnosis 2 years later in a cohort of patients with early arthritis. METHODS: A total of 258 patients with arthritis onset within the previous year were evaluated. At baseline, all patients underwent a standardized evaluation including laboratory tests and radiographs. Hand radiographs were read by a blinded observer who used a standardized procedure for detecting features of crystal deposition diseases and rheumatoid arthritis (RA). After 30 +/- 11.3 months, the final diagnosis was established by a panel of rheumatologists. All radiographs were evaluated. RESULTS: Significant associations were found between radiographic features and a clinical diagnosis of RA, calcium pyrophosphate dihydrate (CPPD) arthritis, and hydroxyapatite arthritis. No radiographic abnormalities suggesting psoriatic arthritis or gout were seen. The sensitivities of hand radiographs for diagnosing CPPD or hydroxyapatite arthritis ranged from 80% to 100%. Baseline hand radiographs suggested the final diagnosis in 31/258 patients, including 21 (22.5%) of the 93 patients with RA, 10 of the 11 (91%) patients with CPPD or hydroxyapatite deposition disease, and none of the patients with other disorders. Sensitivity was 29%, specificity 86.5%, positive predictive value 61%, and negative predictive value 63%. CONCLUSION: In our cohort of patients with recent arthritis, the overall performance of hand radiographs in predicting a diagnosis 2 years later was modest. However, they had an excellent diagnostic value for calcium deposition diseases.

Classification of primary articular chondrocalcinosis.

Based on long-term observations the authors submit a categorization of primary (hereditary and solitary) articular chondrocalcinosis into three different sub-populations. Attention is drawn to the fact that the extent of the qualitative disorder of the articular cartilage, obviously conditioned genetically, is linked with the age factor and determines the quantitative differences of pyrophosphate arthropathy in primary chondrocalcinosis. In young age, as a rule in the third decade, severe polyarticular condrocalcinosis (first sub-population) develops which causes relatively soon invalidity, in middle age (5th and 6th decade) milder condrocalcinosis develops (second sub-population) which combines with extraarticular, tendinous and tissue calcifacations, and finally in advanced age oligoarticular chondrocalcinosis develops (third sub-population) which is usually associated with ankylosing hyperostosis of the spine. Articular chondrocalcinosis (CCA) which we described by this term as a special metabolic arthropathy which occurs in families and solitary and which we defined as a special nosological unit (35, 36,) has become generally known and firmly established in rheumatology. As ensues from numerous publications, primary (idiopathic) CCA which comprises the hereditary and solitary (sporadic) form is characterized by pyrophosphate arthropathy which develops on articular cartilages not damaged by another process (13, 25, 26, 37); on the other hand as secondary CCA we consider pyrophosphate arthropathies which are associated with metabolic, endocrine or other diseases (9, 30). The common sign of both basic forms of CCA is the presence of microcrystals of calcium pyrophosphate dihydrate (CaPD) in articular cartilages, synovial fluid, or other articular structures (capsules, tendons, ligaments), characterized originally by McCarty et al. (11, 18) and later by other authors (2, 23, 27, 32). In addition to semantic (terminological) problems there were also questions of the classification of CCA because, based on an analysis of major groups of patients, it was revealed that there is a varied picture of chondrocalcinosis or pseudogout (18, 19) or deposition disease (17). of calcium pyrophosphate dihydrate crystals. In our paper we are presenting our view on the primary form of CCA and submitting the characteristics of classification which ensued from more than 20 years observation of our group of patients, in particular based on the evaluation of the beginning of the clinical and X-ray manifestations and the further development of the disease.

Crystal arthritis.

Diagnostic and classification criteria have the purpose of separating patients with a certain disease from those without the condition and from normal subjects. Specific identification of the different microcrystals establishes the definite diagnosis of crystal arthritides. The diagnostic criteria for gouty arthritis set up by the American Rheumatism Association in 1975 function well; both their sensitivity and specificity are satisfactory. Unfortunately, we have had no data on the real value of the diagnostic criteria used in CPPD or in hydroxyapatite deposition disease. Status or ranking criteria for stratifying patients by state of disease, such as activity or damage, have not been developed as yet in any type of crystal induced arthropathies. Reliable prognostic criteria sets and outcome criteria are clearly needed to indicate the course of the diseases at the onset, as well as to define the overall impact, of crystal deposition diseases.

[Calcinosis of the meniscus. Morphologic and roentgenographic findings for zonal classification]. / Kalzinosen des Meniskus. Morphologische und röntgenographische Befunde zur zonalen Gliederung.

Primary and secondary meniscal chondrocalcinoses lead to typical changes in X-ray pictures of isolated menisci. Combined X-ray, light and electron microscopic examination of the four menisci in 70 autopsy cases showed calcifications in 13 cases (18.6%). Three types of calcification could be discriminated with the help of topographical and morphological criteria: Type 1 A: disseminated calcification. All four menisci were affected equally. Crystals of calcium pyrophosphate dihydrate (CPPD) were found on light and electron microscopy. Energy-dispersive X-ray analysis (EDX) showed the crystal deposits to consist of 46.5% calcium and 53.5% phosphorus. Type 1 B: Calcification occurring in limited areas. A calcification was found which did affected neither a whole meniscus nor all four menisci of any "quartet" observed. Crystals were found next to areas of stronger meniscal degeneration. EDX showed the same results described for type 1 A. Type 2: Confluent calcification. A cloud-like diffuse calcification was discerned on the X-ray pictures. Light and electron microscopically pseudocystic structures appeared which contained a fine granular amorphous material. No crystals were found. The structures appeared in the neighbourhood of necrotic fibres. EDX showed 44% calcium, 51.2% phosphorus, 2.8% sulphur, 0.74% magnesium and 0.6% potassium. The findings lead to the conclusion that calcification type 1 A represents primary chondrocalcinosis, whereas type 1 B corresponds to secondary chondrocalcinosis. Type 2 was identified as postnecrotic, dystrophic calcification. Careful analysis of X-ray pictures of isolated menisci can yield useful information concerning pathogenetic factors of meniscal calcification.

Diagnóstico por la imagen de la patología del cartílago articular / Diagnostic imaging of articular cartilage disease

El estudio de la patología del cartílago articular se ha desarrollado de forma importante en los últimos años, en parte por la mejora de las técnicas de imagen que la estudian y por la necesidad de una mayor sensibilidad y especificidad para la aplicación de nuevas terapéuticas .La radiología convencional sigue siendo la primera modalidad de estudio para evaluar la patología aguda o crónica del cartílago articular, a pesar de que los datos que aporta son indirectos y de lesiones en estadios avanzados. La resonancia magnética, por su capacidad multiplanar y su mayor contraste tisular, utilizando principalmente secuencias echo de gradiente 3-D o mediante artro-RM directa o indirecta, es la técnica más empleada para obtener resultados adecuados. Este artículo describe las principales técnicas de diagnóstico e ilustra su papel en las patologías más comunes del cartílago como la condromalacia, la patología degenerativa, las alteraciones traumáticas, la osteocondritis disecante y la condrocalcinosis (AU)