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CPPD disease (also called pseudogout) is common, especially among persons older than 60 years of age, but it is underrecognized and undertreated. This review summarizes the diagnosis and treatment of the acute and chronic forms of this crystal-induced arthritis. Calcium pyrophosphate deposition (CPPD) disease is arthritis caused by calcium pyrophosphate (CPP) crystals (Figure 1). Until recently, CPPD disease has been referred to as pseudogout. This term stems from an early description of this disease in patients with an acute goutlike arthritis whose synovial-fluid crystals were resistant to digestion by uricase and who thus did not have gout. 1 Almost simultaneously, a case series was published of 27 patients in Hungary who had chronic episodic inflammatory oligoarthritis affecting primarily the knee. 2 These patients shared a radiographic finding that was characterized by a “dense narrow band following the contour of the epiphysis” . . .

Introduction Pseudogout is characterized by the deposition of calcium pyrophosphate crystals in the pericellular matrix of chondrocytes. Pseudogout flares can present similar to gout, osteoarthritis, septic arthritis, or prosthetic joint infection, potentially complicating post-surgical outcomes. With a high prevalence among patients undergoing arthroplasty, appropriate awareness is essential to mitigate misdiagnosis and inappropriate treatment. This study reviews a series of eight patients in whom white deposits are identified intraoperatively and seeks to guide identification, patient education, and future treatment for pseudogout. Methods Patients undergoing surgical intervention were assessed for the presence of an intraarticular white substance. When the substance was identified, a sample was sent for assessment by a pathologist. The patients’ age, sex, pertinent history, surgery, site of biopsy, and pathologist findings were documented. Results Of the eight patients included in the study, the average age was 67.9 years (range 62–75). Five (62.5%) were male and three (37.5%) were female. Six (75%) were found to have CPPD crystals. Out of these six, one had a steroid injection 5 months prior and another 7 months prior. One patient who had a steroid injection 4 months prior to surgery had a scant amount of white substance that was identified as “acellular material” by the pathologist. Only a single patient of these six had a standing diagnosis of pseudogout prior to surgery. Intraoperatively, the white substances were visually similar in all cases. Conclusions There is a high prevalence of pseudogout in patients over the age of 65 and with concurrent arthritis. Presentation of pseudogout can range from asymptomatic to mimicking septic arthritis. Unidentified white substances noted intraoperatively should be sent to pathology for identification. In patients with pseudogout, it is important to educate the patient and consider prophylactic treatment to minimize risk of recurrence and damage to other joints.

Peri-odontoid calcium pyrophosphate dihydrate deposition (CPPD) results in extradural masses that compress the cervicomedullary junction (CMJ). The authors analyzed their experience in the MRI era to understand causation, radiographic pathology, treatment options, and outcome. Retrospective analysis of University of Iowa Hospitals & Clinics records of retro-odontoid masses consistent with diagnosis of CPPD was made. 46 patients were identified; 21 have been described and 25 now added. Patients underwent cervical motion radiographs, CT, MRI. Postoperative MRI was made in all 25 patients. Mean age was 75.8 years, mean symptom duration 3.6 years. Headache presented in 84 %, myelopathy 92 %, lower cranial nerve dysfunction 36 %, urinary incontinence 36 % and misdiagnosis 52 %. Subaxial pathology (cervical fusion, DISH, lateral mass fusion) with CVJ instability was seen in 92 %. MRI revealed rim enhancement in all and 11 associated cysts. CT calcification in the mass was 96 %, odontoid fractures in 4. Primary ventral transoral resection made in patients with severe neurological deficits. Primary dorsal fixation patients had co-morbidities but showed improvement. Comparison of preoperative and postoperative status and JOA scores reflect the improvements. Pathology proven diagnosis of CPPD was made in 36/46 patients of the entire series. Preoperative diagnosis can be based on retro-odontoid location, absence of MRI enhancement, CT calcifications in the mass and subaxial cervical fixation. Transoral resection of the mass should be reserved for severe CMJ compression. Dorsal C1 decompression and fusion has recently been shown to be satisfactory in others. All patients should be considered as being unstable and must be fused. •CAPPD in the retro-odontoid space is easily misdiagnosed for other pathologies.•Subaxial cervical pathology with craniovertebral instability present in 92 %, calcification 96 %, MRI rim enhancement in all.•CPPD crystals in fresh specimen is critical in diagnosis. Dorsal decompression/fusion is what is required in most cases.

ObjectiveTo summarise current data regarding the use of imaging in crystal-induced arthropathies (CiAs) informing a European Alliance of Associations for Rheumatology task force.MethodsWe performed four systematic searches in Embase, Medline and Central on imaging for diagnosis, monitoring, prediction of disease severity/treatment response, guiding procedures and patient education in gout, calcium pyrophosphate dihydrate deposition (CPPD) and basic calcium phosphate deposition (BCPD). Records were screened, manuscripts reviewed and data of the included studies extracted. The risk of bias was assessed by validated instruments.ResultsFor gout, 88 studies were included. Diagnostic studies reported good to excellent sensitivity and specificity of dual-energy CT (DECT) and ultrasound (US), high specificity and lower sensitivity for conventional radiographs (CR) and CT. Longitudinal studies demonstrated sensitivity to change with regard to crystal deposition by US and DECT and inflammation by US and structural progression by CR and CT. For CPPD, 50 studies were included. Diagnostic studies on CR and US showed high specificity and variable sensitivity. There was a single study on monitoring, while nine assessed the prediction in CPPD. For BCPD, 56 studies were included. There were two diagnostic studies, while monitoring by CR and US was assessed in 43 studies, showing a reduction in crystal deposition. A total of 12 studies with inconsistent results assessed the prediction of treatment response. The search on patient education retrieved two studies, suggesting a potential role of DECT.ConclusionThis SLR confirmed a relevant and increasing role of imaging in the field of CiAs.

ObjectiveTo formulate evidence-based recommendations and overarching principles on the use of imaging in the clinical management of crystal-induced arthropathies (CiAs).MethodsAn international task force of 25 rheumatologists, radiologists, methodologists, healthcare professionals and patient research partners from 11 countries was formed according to the EULAR standard operating procedures. Fourteen key questions on the role of imaging in the most common forms of CiA were generated. The CiA assessed included gout, calcium pyrophosphate deposition disease and basic calcium phosphate deposition disease. Imaging modalities included conventional radiography, ultrasound, CT and MRI. Experts applied research evidence obtained from four systematic literature reviews using MEDLINE, EMBASE and CENTRAL. Task force members provided level of agreement (LoA) anonymously by using a Numerical Rating Scale from 0 to 10.ResultsFive overarching principles and 10 recommendations were developed encompassing the role of imaging in various aspects of patient management: making a diagnosis of CiA, monitoring inflammation and damage, predicting outcome, response to treatment, guided interventions and patient education. Overall, the LoA for the recommendations was high (8.46–9.92).ConclusionsThese are the first recommendations that encompass the major forms of CiA and guide the use of common imaging modalities in this disease group in clinical practice.

Background The aim was to assess serum magnesium levels in relation to prevalence of knee chondrocalcinosis in two population-based Chinese studies. Methods Data included in this analysis consisted of two population-based cross-sectional studies, i.e., the Xiangya Hospital Health Management Center Study and the Xiangya Osteoarthritis (XO) Study I. A bilateral knee anteroposterior radiograph was obtained from each subject. Radiographic knee chondrocalcinosis was present if there was definite linear cartilage calcification. Serum magnesium concentration was measured using the chemiluminescence method. We examined the relation of serum magnesium levels to prevalence of knee chondrocalcinosis using generalized estimating equations. Results The prevalence of knee chondrocalcinosis was 1.4% in the Xiangya Hospital Health Management Center Study (n = 12,631). Compared with the lowest tertile, the age, sex and body mass index (BMI)-adjusted odds ratios (ORs) of chondrocalcinosis were 0.59 (95% CI 0.40–0.87) and 0.49 (95% CI 0.33–0.72) in the second and the third tertiles of serum magnesium, respectively ( P for trend <0.001). The prevalence of knee chondrocalcinosis in the XO Study I (n = 1316) was 4.1%. The age, sex and BMI-adjusted ORs of chondrocalcinosis were 0.67 (95% CI 0.34–1.30) in the second and 0.45 (95% CI 0.21–0.94) in the third tertile of serum magnesium when compared with the lowest tertile ( P for trend = 0.030). Similar results were observed in men and women in both studies. Adjusting for additional potential confounders did not change the results materially. Conclusions Subjects with lower levels of serum magnesium, even within the normal range, had higher prevalence of knee chondrocalcinosis in a dose-response relationship manner, suggesting that magnesium may have a preventive or therapeutic potential for knee chondrocalcinosis.

Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

Polymyalgia rheumatica is an inflammatory condition that affects persons older than 50 years of age and is characterized by pain in both shoulders with or without hip or neck pain (or both) and with pronounced morning stiffness. The condition is typically diagnosed on the basis of these hallmark symptoms along with elevated inflammation markers (erythrocyte sedimentation rate and C-reactive protein level) and the ruling out of other conditions including giant-cell arteritis. Glucocorticoids are the primary treatment, which provide rapid symptom relief. The initial dose, usually 12.5 to 25 mg of prednisone equivalent daily, is gradually reduced, ideally over 12 months or less, although the disease course varies and polymyalgia rheumatica may persist for a longer duration. Relapses are common and sometimes warrant the use of interleukin-6 receptor inhibitors or methotrexate to minimize glucocorticoid exposure. This review summarizes the diagnosis and management of polymyalgia rheumatica in adults older than 50 years of age, emphasizing clinical diagnosis, glucocorticoids as first-line therapy, relapses, and glucocorticoid-sparing options.

The first line of defence The inflammasome is a complex of proteins involved in the activation of the innate immune system, an evolutionarily ancient antimicrobial defence found in most multicelled animals. When activated the inflammasome sets in motion a cascade of events that leads to the production of active molecules including interleukins. Three papers in this issue report the identification of endogenous danger signals and bacterial components that activate inflammasomes containing cryopyrin (also known as NALP3). Mariathasan et al . show that cryopyrin activates the inflammasome in response to bacterial toxins and to ATP. Kanneganti et al . show that cryopyrin is activated by bacterial RNA and by the immune response modifiers R837 and R848. And Martinon et al . show that gout-associated uric acid crystals have a similar effect. In sum these results show that cryopyrin has a vital role in host antibacterial defences and may act as a sensor of cellular stress. In addition, this work provides insight into the mechanisms of autoinflammatory disorders in which abnormalities in the innate immune system have been implicated. Development of the acute and chronic inflammatory responses known as gout and pseudogout are associated with the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and periarticular tissues. Although MSU crystals were first identified as the aetiological agent of gout in the eighteenth century 1 and more recently as a ‘danger signal’ released from dying cells 2 , little is known about the molecular mechanisms underlying MSU- or CPPD-induced inflammation. Here we show that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1β and IL-18. Macrophages from mice deficient in various components of the inflammasome such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1β activation. Moreover, an impaired neutrophil influx is found in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient in the IL-1β receptor (IL-1R). These findings provide insight into the molecular processes underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases.