Pseudogout Research Articles

Prevalence of chondrocalcinosis and calcium pyrophosphate deposition disease in a cohort of adult patients with low alkaline phosphatase levels and a positive versus negative genetic ALPL study.

To estimate the prevalence of chondrocalcinosis and calcium pyrophosphate dihydrate deposition disease (CPPD) in patients with low alkaline phosphatase (ALP) levels and a positive ALPL genetic study (+GT) for hypophosphatasia (HPP) compared to those with the same biochemical abnormality and a negative genetic test (-GT). As a secondary objective, to analyze the biochemical factors associated with its presence in subjects with ALPL variants. Seventy-eight subjects with persistently low ALP levels and ALPL genetic test were included. Baseline and 24-mo knee ultrasounds were performed in 42 + GT and 36 -GT subjects, in whom the fibrocartilage, hyaline cartilage of menisci, tendons, and synovial fluid were scanned to detect calcium pyrophosphate deposits. A MyLabTwice ultrasound machine (Esaote) with a multifrequency linear array transducer (4-13MHz) was used. A higher percentage of chondrocalcinosis was observed in the +GT group [9/42 (21.4%)] compared to the -GT group [2/36 (5.6%), p=.045)]. Two patients (4.76%), both in the +GT group, had arthritis secondary to CPPD. No new cases were identified at the 24-mo control. When comparing +GT patients with and without chondrocalcinosis, ALP levels were lower, and pyridoxal-5'-phosphate (PLP) and phosphate levels were higher in the former group (p<.05). Logistic regression analysis revealed that higher PLP levels are associated with the presence of chondrocalcinosis (OR: 1.1; 95% confidence interval, CI, 1.001-1.012). Chondrocalcinosis was a frequent ultrasonographic finding in HPP. Arthritis secondary to calcium pyrophosphate deposits, however, proved less prevalent. Genetic causes, such as HPP, should be considered when evaluating patients with chondrocalcinosis in clinical practice.

Concurrent Post-Zoster Cutaneous Vasculitis and Acute Calcium Pyrophosphate Deposition Disease (CPPD) in an Elderly Patient: A Case Report

Concurrent Post-Zoster Cutaneous Vasculitis and Acute Calcium Pyrophosphate Deposition Disease (CPPD) in an Elderly Patient: A Case Report

Dynamic ultrasonography helps diagnose calcium pyrophosphate deposition disease.

Dynamic ultrasonography helps diagnose calcium pyrophosphate deposition disease.

Calcium Pyrophosphate Deposition Disease: Diagnosis and Treatment

Calcium Pyrophosphate Deposition Disease: Diagnosis and Treatment

Practical Use of Ultrasound in Modern Rheumatology-From A to Z.

During the past 20 years, the use of ultrasound (US) in rheumatology has increased tremendously, and has become a valuable tool in rheumatologists' hands, not only for assessment of musculoskeletal structures like joints and peri-articular tissues, but also for evaluation of nerves, vessels, lungs, and skin, as well as for increasing the accuracy in a number of US-guided aspirations and injections. The US is currently used as the imaging method of choice for establishing an early diagnosis, assessing disease activity, monitoring treatment efficacy, and assessing the remission state of inflammatory joint diseases. It is also used as a complementary tool for the assessment of patients with degenerative joint diseases like osteoarthritis, and in the detection of crystal deposits for establishing the diagnosis of metabolic arthropathies (gout, calcium pyrophosphate deposition disease). The US has an added value in the diagnostic process of polymyalgia rheumatica and giant-cell arteritis, and is currently included in the classification criteria. A novel use of US in the assessment of the skin and lung involvement in connective tissue diseases has the potential to replace more expensive and risky imaging modalities. This narrative review will take a close look at the most recent evidence-based data regarding the use of US in the big spectrum of rheumatic diseases.

An objective diagnosis of gout and calcium pyrophosphate deposition disease with machine learning of Raman spectra acquired in a point-of-care setting.

Raman spectroscopy is proposed as a next-generation method for the identification of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid. As the interpretation of Raman spectra requires specific expertise, the method is not directly applicable for clinicians. We developed an approach to demonstrate that the identification process can be automated with the use of machine learning techniques. The developed system is tested in a point-of-care-setting at our outpatient rheumatology department. We collected synovial fluid samples from 446 patients with various rheumatic diseases from three centra. We analyzed all samples with our Raman spectroscope and used 246 samples for training and 200 samples for validation. Trained observers classified every Raman spectrum as MSU, CPP or else. We designed two one-against-all classifiers, one for MSU and one for CPP. These classifiers consisted of a principal component analysis model followed by a support vector machine. The accuracy for classification of CPP using the 2023 ACR/EULAR CPPD classification criteria was 96.0% (95% CI 92.3-98.3), while the accuracy for classification of MSU with using the 2015 ACR/EULAR gout classification criteria was 92.5% (95% CI 87.9-95.7). Overall, the accuracy for classification of pathological crystals was 88.0% (95% CI 82.7-92.2). The model was able to discriminate between pathologic crystals, artifacts, and other particles such as microplastics. We here demonstrate that potentially complex Raman spectra from clinical patient samples can be successfully classified by a machine learning approach, resulting in an objective diagnosis independent of the opinion of the medical examiner.

Distal interphalangeal joint involvement in patients with rheumatoid arthritis: Where are we?

Rheumatoid arthritis (RA) usually affects the wrist, metacarpophalangeal joint, and proximal interphalangeal joint of the hands. However, the distal interphalangeal (DIP) joints may also be involved in RA patients. In this study, we aimed to evaluate the frequency and associated factors of DIP joint erosion in patients with RA. Medical records of patients with RA were reviewed retrospectively. Patients with major trauma affecting DIP joints, osteoarthritis, erosive osteoarthritis, psoriatic arthritis, systemic sclerosis, calcium pyrophosphate dihydrate disease, and gout were excluded. Anteroposterior hand X-rays were evaluated and patients were divided into groups according to autoantibody profile. We reviewed 1213 patients with a mean age of 54.3 ± 12.5 years; 82.8% of them were female, and 95.4% had RA-type erosive changes. The DIP erosion rate was 12%. DIP involvement was generally unilateral and asymmetric, with the 3rd finger being the most commonly affected joint. Patients with DIP erosions had a significantly longer disease duration (p = 0.036). Older age was an independent predictive factor for DIP erosion (p = 0.001). In this large-sample study, we reported DIP joint involvement in patients with RA. Advanced age could have affected the results because hand erosions increase above 50 years in a healthy population. Our results may provide a different perspective on joint involvement in RA.

Calcium Pyrophosphate Crystal Deposition: Insights to Risks Factors and Associated Conditions.

This review provides an overview of medical conditions and risk factors associated with CPPD. Recent studies have indicated that CPPD patients may have a higher risk for systemic conditions such as cardiovascular diseases. Calcium pyrophosphate deposition disease (CPPD) is a common crystal arthropathy that primarily affects older adults, and, in most cases, the aetiology is idiopathic. Age is the most remarkable risk factor and due to the aging population, the prevalence of this condition is expected to increase. Strong evidence supports an association between CPPD and several metabolic and endocrine conditions, including hemochromatosis, hyperparathyroidism, hypomagnesemia, and hypophosphatasia. Additionally, there is growing evidence of an increased risk for cardiovascular diseases among CPPD patients, alongside potential links to rheumatic disorders, gender, medications, and joint trauma. Further research is needed to explore the underlying mechanisms linking CPPD to associated conditions and to develop targeted therapies with the aim of improving patient outcomes.

Features Associated With Different Inflammatory Phenotypes of Calcium Pyrophosphate Deposition Disease: Study Using Data From the International American College of Rheumatology/EULAR Calcium Pyrophosphate Deposition Classification Criteria Cohort.

The study objective was to examine the disease, demographic, and imaging features associated with different inflammatory phenotypes of calcium pyrophosphate deposition (CPPD) disease, ie, recurrent acute calcium pyrophosphate (CPP) crystal arthritis, chronic CPP crystal inflammatory arthritis, and crowned dens syndrome (CDS). Data from an international cohort (assembled from 25 sites in 7 countries for the development and validation of the 2023 CPPD classification criteria from the American College of Rheumatology/EULAR) that met the criteria were included. Three cross-sectional studies were conducted to determine the phenotypic characteristics of recurrent acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and CDS. Multivariable logistic regression analysis was used to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI) to examine the association between potential risk factors and the inflammatory phenotype. Among the 618 people included (56% female; mean age [standard deviation] 74.0 [11.9] years), 602 (97.4%) had experienced acute CPP crystal arthritis, 332 (53.7%) had recurrent acute arthritis, 158 (25.6%) had persistent inflammatory arthritis, and 45 (7.3%) had had CDS. Recurrent acute CPP crystal arthritis associated with longer disease duration (aOR 2.88 [95% CI 2.00-4.14]). Chronic CPP crystal inflammatory arthritis was associated with acute wrist arthritis (aOR 2.92 [95% CI 1.81-4.73]), metacarpophalangeal joint osteoarthritis (aOR 1.87 [95% CI 1.17-2.97]), and scapho-trapezo-trapezoid (STT) joint osteoarthritis (aOR 1.83 [95% CI 1.15-2.91]), and it was negatively associated with either metabolic or familial risk for CPPD (aOR 0.60 [95% CI 0.37-0.96]). CDS was associated with male sex (aOR 2.35 [95% CI 1.21-4.59]), STT joint osteoarthritis (aOR 2.71 [95% CI 1.22-6.05]), and more joints affected with chondrocalcinosis (aOR 1.46 [95% CI 1.15-1.85]). CPPD disease encompasses acute and chronic inflammatory phenotypes, each with specific clinical and imaging features that need to be considered in the diagnostic workup.

Pathology on caudal vertebra of Glyptodon sp. (Xenarthra, Cingulata) from the Upper Pleistocene (Luján Formation) of Buenos Aires province (Argentina)

The paleontological collection of the Museo Municipal de Ciencias Naturales “Carlos Ameghino” (MCA, Mercedes, Buenos Aires Province, Argentina) includes hundreds of mammalian fossil specimens collected from the Luján Formation (Lujanian Stage/Age), bounded to the Late Pleistocene/Early Holocene. Among the specimens of the MCA collection, a caudal vertebra (MCA-117) of Glyptodon sp. (Xenarthra, Cingulata) with pathologies was identified, which are here characterized in order to perform a diagnosis. The main alterations in the vertebra consist of bone erosion and remodeling in the left transverse process, bone erosion in the vertebral centrum, and deformation in the neural arch affecting the prezygapophyses. The features identified in the transverse process were diagnosed as bone remodeling, alterations previously described for Pleistocene xenarthrans. The erosions observed in the vertebral centrum are comparable to spondylosis, Schmorl's node, intervertebral discopathies, or, alternatively, calcium pyrophosphate deposition disease. Nonetheless, these could potentially manifest as secondary complications arising from spondylosis. Regarding characteristics such as low bone density, it is concluded that they are indicative of modifications due to osteoporosis. The alterations present in the specimen can be compared with bone pathologies recognized in elderly individuals with large body mass.

Treatment strategies for calcium pyrophosphate deposition disease

Treatment strategies for calcium pyrophosphate deposition disease

Calcium pyrophosphate deposition disease: points to be considered for quality assurance in clinical practice

Calcium pyrophosphate deposition disease: points to be considered for quality assurance in clinical practice

Progression of arthritis after four-corner fusion in patients with calcium pyrophosphate deposition disease: a case series of eleven patients

Aim: The purpose of this study is to evaluate outcomes and radiographic progression of wrist arthritis after four-corner fusion (4CF) in patients with evidence of calcium pyrophosphate deposition disease (CPPD). The insights derived from this study are expected to improve the understanding of 4CF outcomes in the presence of CPPD, guiding clinical decisions, and management strategies. Methods: 11 patients with prior 4CF and evidence of CPPD were available for prospective follow-up and imaging, with a mean follow-up time of 5 years. Range of motion measurements, radiographs, and outcome data were collected at the follow-up visit and prior data and imaging were reviewed retrospectively. The chronological progression of arthritis was evaluated on standard three-view wrist radiographs using the Larsen scale. Results: All participants (11/11) deemed their wrist fusion a success, with an average satisfaction score of 8.8 out of 10.73% (8/11) patients were able to return to their original occupation after the procedure. The mean flexion of the affected wrist preoperatively was 43 degrees (SD: ±12 degrees) and 41 degrees (SD: ±7 degrees) at the final follow-up. The mean extension of the affected wrist was 35 degrees (SD: ±8 degrees) preoperatively and 40 degrees (SD: ±12 degrees) at the final follow-up. Radiographic analysis showed that 82% (9/11) of patients displayed progression of arthritis as per the Larsen scale by the final follow-up. All patients that showed radiographic progression had involvement of the radiolunate (RL) articulation, which is classically persevered in non-inflammatory wrist arthritis. Conclusions: Scaphoid excision with 4CF is a promising surgical option for managing CPPD-related wrist arthritis, offering significant functional improvements, motion preservation, and high patient satisfaction. However, it does not halt radiographic progression of arthritis for the majority of patients at a mean prospective long-term follow-up of 5 years.

The translational value of calcium pyrophosphate deposition disease experimental mouse models

The deposition of calcium pyrophosphate (CPP) crystals in joint tissues causes acute and chronic arthritis that commonly affect the adult and elderly population. Experimental calcium pyrophosphate deposition disease (CPPD) models are divided into genetically modified models and crystal-induced inflammation models. The former do not reproduce phenotypes overlapping with the human disease, while in the latter, the direct injection of crystals into the ankles, dorsal air pouch or peritoneum constitutes a useful and reliable methodology that resembles the CPP induced-inflammatory condition in humans. The translational importance of the induced model is also strengthened by the fact that the key molecular and cellular mediators involved in inflammation are shared between humans and laboratory rodents. Although, in vivo models are indispensable tools for studying the pathogenesis of the CPPD and testing new therapies, their development is still at an early stage and major efforts are needed to address this issue. Here, we analyze the strenghts and limitations of each currently available CPPD in vivo model, and critically discuss their translational value.

Acute coronary syndrome in calcium pyrophosphate deposition disease patients: A US inpatient care cohort study

ObjectiveRecent studies have shown that CPPD might be associated with a higher risk of cardiovascular events related to inflammation. Thus, we aim to examine the outcomes of patients admitted for acute coronary syndrome (ACS) with and without CPPD. MethodsWe used data from the US National Inpatient Sample (NIS) Database to identify patients who were admitted for ACS between 2006 and 2019. The ICD-9 and -10 codes were used to determine the patients with ACS related hospitalizations and of those, we classified two groups of patients: those with and those without any CPPD code. Data collection included demographics and comorbidities. Outcomes were in-hospital mortality, length of stay, hospital charges, and in-hospital complications. Associations between CPPD and specific morbidity were evaluated with chi-square tests. T-tests were used for continuous variables. We have also presented odds ratio (OR) along with 95 % confidence intervals (CI) for the outcomes of interest. ResultsA total of 17,322,362 patients were admitted for ACS. Among them, 7,458 had CPPD, with a mean age of 75 years and 48 % were females. CPPD patients were more likely to be older (75 vs 68 years; p < 0.001) compared to non-CPPD patients. Among the comorbidities, chronic kidney disease was more frequently observed in CPPD patients. Regarding the inpatient complications, acute ischemic stroke and post-procedural hemorrhage were more frequently seen in CPPD patients. Interestingly, the in-hospital mortality was lower in the CPPD patients than the non-CPPD patients (OR: 0.77; CI 95 % 0.70–0.85). ACS in CPPD patients was associated with a longer mean length of stay than those without CPPD (OR: 3.35; 95 % CI 3.17–3.53). In addition, mean total charges were higher in the CPPD group (OR: 1.04; 95 % CI 1.01–1.10). ConclusionACS in CPPD patients is associated with higher healthcare utilization, including cost and length of hospital stay, and lower in-hospital mortality than non-CPPD patients

A Narrative Review of Chondrocalcinosis: Clinical Presentation, Diagnosis, and Therapies.

Calcium pyrophosphate deposition disease is categorized into radiographic chondrocalcinosis, acute calcium pyrophosphate arthritis, chronic calcium pyrophosphate arthritis, and osteoarthritis with calcium pyrophosphate deposition. These entities collectively are characterized by the deposition of calcium into joints, which then may cause localized and systemic inflammation, resulting in pain and swelling in the affected joints. Patients with the ANKH gene are more susceptible to the development of CPP arthritis as are those with primary hyperparathyroidism, hypomagnesemia, and hemochromatosis. Radiographic chondrocalcinosis is asymptomatic. Acute calcium pyrophosphate arthritis results in self-limited periods of joint pain and swelling in the affected joint. Along with localized inflammation, there may also be systemic inflammation characterized by fever and elevated inflammatory markers. Chronic calcium pyrophosphate arthritis results in periods of quiescence interrupted by flares that are identical to acute periods of disease. Osteoarthritis associated calcium pyrophosphate arthritis presents with chronic pain well described in osteoarthritis with periods of acute flares. In 2023, a joint effort by the American College of Rheumatology and the European League Against Rheumatism developed guidelines meant to aid in the recognition of calcium pyrophosphate deposition diseases. The diagnosis is made if there is proof of either crowned dens syndrome or synovial fluid analysis demonstrating calcium pyrophosphate crystals or when more than 56 points are summed utilizing the criteria described in the guidelines. Radiographic chondrocalcinosis requires no therapy. Acute calcium pyrophosphate arthritis is treated with the goal of aborting the flare. Treatment options include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, oral corticosteroids, parenteral corticosteroids, intraarticular corticosteroids, IL-1 inhibitors, or parenteral adrenocorticotropic hormone (ACTH). The goal in treatment for chronic calcium pyrophosphate arthritis is the suppression of acute flares. The drugs used for acute flare treatment may be given as maintenance therapy with the additional options of methotrexate and hydroxychloroquine.

Full endoscopic surgery for calcium pyrophosphate deposition disease (CPPD) in the cervical ligamentum flavum: report of two cervical myelopathy cases.

Calcium pyrophosphate deposition disease (CPPD), known as pseudogout, is characterized by the accumulation of calcium pyrophosphate crystals in musculoskeletal structures, primarily joints. While CPPD commonly affects various joints, involvement in the cervical spine leading to myelopathy is rare. Surgical intervention becomes necessary when conservative measures fail, but reports on full endoscopic surgeries are extremely rare. We present two successful cases where full endoscopic systems were used for CPPD removal in the cervical spine. The surgical technique involved a full endoscopic approach, adapting the previously reported technique for unilateral laminotomy bilateral decompression. Full-endoscopic removal of cervical CPPD inducing myelopathy were successfully removed with good clinical and radiologic outcomes. The scarcity of endoscopic cases for cervical ligamentum flavum CPPD is attributed to the condition's rarity. However, our successful cases advocate for endoscopic surgery as a potential primary treatment option for CPPD-induced cervical myelopathy, especially in elderly patients or those with previous cervical operation histories. This experience encourages the consideration of endoscopic surgery for managing cervical ligamentum flavum CPPD as a viable alternative.

Calcium Pyrophosphate and Basic Calcium Phosphate Crystal Arthritis: 2023 in Review

Calcium-containing crystal deposition diseases are extremely common in rheumatology. However, they are under-explored compared to gout or other inflammatory rheumatic diseases. Major advances have been made in 2023 that will undoubtedly stimulate and facilitate research in the field of calcium pyrophosphate (CPP) deposition disease (CPPD): the ACR/EULAR classification criteria for CPPD and a semi-quantitative OMERACT score for ultrasound assessment of the extent of CPP deposition have been validated and published. A large randomized controlled trial compared the efficacy and safety of colchicine and prednisone in acute CPP arthritis. Preclinical studies have elucidated the pro-inflammatory and anti-catabolic effects of basic calcium phosphate (BCP) crystals on mononuclear cells and chondrocytes. The association between osteoarthritis (OA) and IA calcifications has been the subject of several epidemiological publications, suggesting that calcium crystals are associated with a greater risk of progression of knee OA. Research in the field of calcium crystal deposition diseases is active: the areas of investigation for the coming years are broad and promising.

Calcium pyrophosphate deposition disease: historical overview and potential gaps.

CPPD disease can affect patients’ quality of life through its various clinical presentations. This mini-review discusses the evolution of CPPD from its discovery to current knowledge of its pathogenesis, genetic associations, diagnostics, and treatment options. Despite extensive research, the exact mechanisms of CPPD are not well understood, and there is a notable lack of knowledge about psychosocial impacts and patient experiences. This study aims to present a CPPD Disease Timeline identifying gaps in current knowledge and potential directions for future research. These findings contribute to a broader understanding of CPPD disease and emphasize the importance of continued research and innovation in this field.

Middle Ear Tophi: A Case Series of Two Unusual Lesions and a Report of Facial Weakness and Review of the Literature.

Tophaceous lesions of the middle ear from calcium pyrophosphate deposition disease (CPPD, or pseudogout) and gout are infrequently reported. Recognizing its characteristic findings will allow clinicians to accurately narrow the differential diagnosis of bony-appearing middle ear lesions and improve management. Two consecutive cases of tophaceous middle ear lesions presenting to a tertiary care center between January 2021 and December 2021. Neither with previous rheumatologic history. Surgical excision of tophaceous middle ear lesions. Improvements in facial weakness and conductive hearing loss. The first case was a 66-year-old gentleman with progressive conductive loss, ipsilateral progressive facial weakness over years, and an opaque, irregular-appearing tympanic membrane anterior to the malleus found to have CPPD on surgical pathology, with immediate postoperative improvement of facial function. The second was a 75-year-old gentleman with progressive conductive loss and similar appearing tympanic membrane as case 1, previously diagnosed with tympanosclerosis, found to have gout on surgical pathology. In both cases, the CT showed a heterogenous, bony-appearing lesion in the middle ear, and both tophaceous lesions were a of gritty, chalky consistency intraoperatively. Tophaceous lesions of the middle ear are rare but have similar findings. Notably, the tympanic membrane can appear opaque and irregular, and the CT demonstrates a radiopaque, heterogeneous appearance. Facial weakness is an unusual finding. Specimens of suspected tophi must be sent to pathology without formalin for accurate diagnosis.