Pseudogout Research Articles

CT imaging features of calcium pyrophosphate dihydrate crystal deposition involving spine

PurposeTo explore the computed tomography (CT) imaging features of the spine involved by calcium pyrophosphate dihydrate crystal deposition disease (CPPD-CDD) in order to improve the understanding of this disease. Materials and methodsAmong 79 patients diagnosed with CPPD-CDD in our hospital, 51 patients with spinal involvement were selected, 9 patients without CT examination were excluded, and 42 patients were finally included as research objects. The CT images of the 42 patients were retrospectively analyzed. The analysis contents mainly included the distribution of lesions and the characteristic imaging findings of intervertebral disc, posterior ligament complex, sacroiliac joint and atlantoaxial joint. ResultsIn this paper, 42 patients with 11 males and 31 females were studied. The onset age ranged from 62 to 95 years. There were 264 lesions in 42 patients with spinal involvement, including 177 lumbar vertebrae, 43 cervical vertebrae, 27 thoracic vertebrae and 17 sacroiliac joints (14 bilateral and 3 unilateral). Characteristic imaging findings include: disc calcification (129 cases), posterior ligament complex calcification (107 cases), sacroiliac articular cartilage calcification (17 cases), and ligaments around the odontoid process calcification (11 cases). ConclusionsThe characteristic images of CPPD-CDD involving the spine are calcification of intervertebral disc, posterior ligament complex, sacroiliac joint surface and ligaments around odontoid process, and the lesions are frequent and coexisting, so it should be differentiated from gout, rheumatoid arthritis, ankylosing spondylitis, ossification of ligamentum flavum, basic calcium phosphate and infectious spondylodiscitis.

Recent advances in the therapeutic management of calcium pyrophosphate deposition disease.

Calcium pyrophosphate deposition (CPPD) disease is a form of crystal-induced arthropathy that arises from the accumulation of calcium pyrophosphate crystals within joints and soft tissues. This process leads to inflammation and damage to the affected joints. It can present asymptomatically or as acute or chronic inflammatory arthritis. Risk factors and comorbidities, including prior joint injury, osteoarthritis, hereditary or familial predisposition, and metabolic diseases, should be evaluated in CPPD cases. The management of CPPD remains a challenge in the sparsity of randomized controlled trials. The lack of such trials makes it difficult to establish evidence-based treatment protocols for CPPD. This review provides an overview of the current pharmacological management of CPPD, focusing on reducing inflammation, alleviating symptoms, and preventing acute flares. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and colchicine are effective in managing acute CPP arthritis. Colchicine may also be used prophylactically to prevent recurrent flares. In cases where other treatments have failed, anakinra, an interleukin-1 receptor antagonist, can be administered to alleviate acute flares. The management of chronic CPP inflammatory arthritis includes NSAIDs and/or colchicine, followed by hydroxychloroquine, low-dose glucocorticoids, and methotrexate, with limited data on efficacy. Tocilizumab can be used in refractory cases. In small studies, synovial destruction using intra-articular injection of yttrium 90 can decrease pain. To date, no disease-modifying therapies exist that reduce articular calcification in CPPD.

First classification criteria for diseases caused by calcium pyrophosphate deposition (CPPD)-Translation, explanation and assessment

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. 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. 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). 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.

Fractures in Patients With Acute Calcium Pyrophosphate Crystal Arthritis Versus Matched Comparators in a Large Cohort Study.

Calcium pyrophosphate deposition (CPPD) disease was associated with osteopenia in two cross-sectional studies. We compared fracture risks in patients with acute calcium pyrophosphate (CPP) crystal arthritis versus matched comparators. We performed a longitudinal cohort study using electronic health record data from a single large academic health system, with data from 1991 to 2023. Patients with one or more episodes of acute CPP crystal arthritis were matched to comparators on the index date (first documentation of "pseudogout" or synovial fluid CPP crystals or matched encounter) and first encounter in the health system. The primary outcome was first fracture at the humerus, wrist, hip, or pelvis. We excluded patients with fracture before the index date. Covariates included demographics, body mass index, smoking, comorbidities, health care use, glucocorticoids, and osteoporosis treatments. We estimated incidence rates and adjusted hazard ratios for fracture. Sensitivity analyses excluded patients prescribed glucocorticoids, patients prescribed osteoporosis treatments, or patients with rheumatoid arthritis and additionally adjusted for chronic kidney disease. We identified 1,148 patients with acute CPP crystal arthritis matched to 3,730 comparators, with a mean age of 73 years. Glucocorticoids and osteoporosis treatments were more frequent in the acute CPP crystal arthritis cohort. Fracture incidence rates were twice as high in the acute CPP crystal arthritis cohort (11.7 per 1,000 person-years) versus comparators (5.5 per 1,000 person-years). After multivariable adjustment, fracture relative risk was twice as high in the acute CPP crystal arthritis cohort (hazard ratio 1.8 [95% confidence interval 1.3-2.3]); results were similar in sensitivity analyses. In this first published study of fractures and CPPD, fracture risk was nearly doubled in patients with acute CPP crystal arthritis.

A New Era for Calcium Pyrophosphate Deposition Disease Research: The First-Ever Calcium Pyrophosphate Deposition Disease Classification Criteria and Considerations for Measuring Outcomes in Calcium Pyrophosphate Deposition Disease

Calcium pyrophosphate deposition (CPPD) disease is a crystalline arthritis that was described more than 60 years ago, yet our knowledge about this condition greatly lags behind other forms of arthritis. This is an exciting era for CPPD disease as a robust framework for CPPD clinical research has been established. The American College of Rheumatology (ACR) and EULAR co-sponsored the development of the first-ever classification criteria for CPPD. The Outcomes Measures in Rheumatology (OMERACT) CPPD Ultrasound Subtask Force developed and validated definitions for ultrasonographic findings of CPPD, and the OMERACT CPPD Working Group is establishing a core outcome domain set for this crystalline arthritis. This review focuses on key elements of the 2023 ACR/EULAR CPPD disease classification criteria and considerations for measuring outcomes in CPPD disease.

Safety and efficacy of colchicine in crystal-induced arthritis flare in 54 patients with severe chronic kidney disease

IntroductionColchicine, commonly used in gout flare, is contraindicated in severe chronic kidney disease (CKD) (estimated glomerular filtration rate <30 mL/min). However, in this context, there are few alternatives, and colchicine...

Diagnosis, Treatment, and Outcomes of Crystalline Arthropathy in the Setting of Total Knee Arthroplasty: A Critical Analysis Review.

» Emerging evidence suggests the prevalence of crystalline arthropathy (CA) in the setting of total knee arthroplasty (TKA) is increasing, and diagnosis of CA is often intricate because of symptom overlap with other common postoperative complications such as periprosthetic joint infection (PJI). Consequently, an accurate and timely diagnosis becomes pivotal in guiding the choice of treatment.» CA includes gout and calcium pyrophosphate deposition (CPPD) disease, and accurate diagnosis in patients with prior TKA requires a multifaceted approach. The diagnosis algorithm plays a critical role in determining the appropriate treatment approach.» Management of CA typically involves a conservative strategy, encompassing the administration of nonsteroidal anti-inflammatory drugs, colchicine, and steroids, regardless of whether patients have undergone prior TKA.» There is conflicting evidence on the effect CA has on the surgical outcomes in postoperative TKA patients. While these patients may expect excellent functional outcomes and pain relief, they may be at a higher risk of complications such as infections, medical complications, and revision procedures.» Additional research is required to fully comprehend the impact of CA on postoperative TKA outcomes and to establish effective strategies for enhancing patient care and optimizing long-term joint function.

Colchicine: the good, the bad, the ugly and how to minimize the risks.

Colchicine has an important role in managing various conditions, including gout, familial Mediterranean fever, amyloidosis, Behçet's syndrome, recurrent pericarditis and calcium pyrophosphate deposition disease. The adverse effect profile of colchicine is well understood. However, due to its narrow therapeutic index, colchicine has been associated with overdose and fatalities. When ingested in toxic amounts, the mainstay of management is supportive care. Strategies to minimize the risk of colchicine poisoning can focus on three broad causes: unauthorized access, intentional overdose and inappropriate dosing. Culturally safe and appropriate education about storage and appropriate use of colchicine is essential to minimize the risk of overdose.

Outcomes of total hip arthroplasty in calcium pyrophosphate deposition disease patients

ObjectiveWe aim to examine the demographics, clinical characteristics, outcomes, and resource utilization following total hip arthroplasty (THA) in patients with and without calcium pyrophosphate deposition (CPPD) disease. MethodsWe queried the National Inpatient Sample database to identify patients who underwent THA between 2006 and 2014. The ICD-9 code 81.51 was used to determine the patients who underwent THA, and of those, we classified 2 groups of patients: (i) those with ICD-9 codes defining CPPD and (ii) those without any CPPD code. Data collection included patient demographics and comorbidities. Outcomes post-THA were mortality, length of stay (LOS), and costs. Associations between CPPD and specific morbidity were evaluated with chi-square tests. T tests were used for continuous variables. ResultsAmong the 4,111,808 patients who underwent THA, 6198 (0.15 %) had CPPD, with a mean age of 77 years and 64.2 % were females. CPPD patients were more likely to be older (mean age 77 vs 72.7 years; p<0.001) than non-CPPD patients. The Charlson Comorbidity Index score ≥ 2 was more frequently seen in CPPD, however, the mortality post-THA was lower in the CPPD patients (0.7 % vs 1.7 %, OR 0.35, 95 % CI 0.26- 0.47). THA in CPPD patients was associated with a longer mean length of stay (LOS) (6.04 vs 5.15 days, OR 1.15, 95 % CI 1.09–1.22) while mean total charges were not statistically different between the 2 groups (p = 0.344). CPPD patients were more likely to be discharged to rehabilitation or other nursing facilities (42.5 % vs 35.3 %, p<0.001). The number of THA procedures increased in both CPPD and non-CPPD patients over time. ConclusionsCPPD patients who underwent THA were more likely to be older, with a greater comorbidity burden, longer LOS and discharged to a non-home setting.

Crystal Diseases of the Spine.

Gout, calcium pyrophosphate deposition disease, and apatite calcifications, the three main crystal disorders, may involve the spine. These disorders can be completely asymptomatic or associated with various clinical symptoms, such as acute flares and more chronic manifestations. This article presents the typical and more unusual imaging features encountered in these disorders.

Pyrophosphate arthropathy — a literature review

Pyrophosphate arthropathy — a literature review

Calcium pyrophosphate deposition disease moves into the spotlight.

Calcium pyrophosphate deposition disease moves into the spotlight.

Four-dimensional computed tomography detects dynamic three-dimensional pathologies of the wrist in patients with calcium pyrophosphate deposition disease.

Crystal deposits in ligaments of the wrist are typical findings in patients with calcium pyrophosphate deposition (CPPD) disease. CPPD crystals trigger inflammation and ultimately result in ligament tears with scapholunate (SL) advanced collapse (SLAC). This study aimed to investigate carpal instabilities in patients with CPPD using four-dimensional computed tomography (4D-CT) of the wrist. This IRB-approved prospective feasibility study investigated patients with CPPD of the hand. All patients underwent a static 3D-CT and two dynamic 4D-CT in ulnar- and radial abduction and in supination and pronation movements to analyze instabilities of the SL region and of the distal radioulnar joint (DRUJ). Two independent readers scored the images for the presence of SL ligament and triangular fibrocartilage complex (TFCC) calcifications. Furthermore, the readers assessed the dynamic images for SL and DRUJ instabilities. Descriptive analyses were performed. Inter-rater reliability was assessed using Cohen's kappa (κ). Nine patients were included. SL ligament calcifications and instabilities were found in all patients. Of these, dynamic SL instability was detected in 77.8% of the patients, while 22.2% had a SLAC wrist. TFCC calcifications were found in 87.5% of the patients. Four patients had DRUJ instability (50%). No patient showed DRUJ instability without the presence of TFCC calcifications. Agreement between readers for calcifications was excellent (κ = 1) and almost perfect (κ = 0.89) for instabilities. This study provides the first evidence of relevant dynamic carpal instability in CPPD patients using advanced imaging techniques with 4D-CT, offering unique insights into wrist biomechanics.

The 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease.

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.

Synovial fluid crystal analysis with compensated polarization using a gout analyser inclinical practice.

To validate the gout analyzer as a clinical method of synovial fluid crystal analysis. Thirty knee synovial fluid samples with suspected calcium pyrophosphate (CPP) crystals were analyzed. Within 48 hours after collection, each non-centrifuged sample was examined blindly and independently by one or more rheumatologists in the following order: 1) with an optical microscope under ordinary light, 2) with the same microscope under compensated polarization provided by a gout analyzer, and 3) with a fully equipped compensated polarized microscope with a rotating stage as the gold standard. As a reference, laboratory technicians analyzed fresh, centrifuged synovial fluid using a gout analyzer. Of the 30 samples analyzed, CPP and monosodium urate (MSU) crystals were detected in 11 and four, non-centrifuged samples, respectively, using a fully equipped compensated polarized microscope. The rheumatologists' detection rate of crystals in the non-centrifuged synovial fluid under ordinary light and with a gout analyzer was 73.3% and 80%, respectively. The laboratory technicians' detection rate in fresh centrifuged synovial fluid using a gout analyzer was 100%. A gout analyzer may be used to diagnose gout and calcium pyrophosphate deposition disease definitively if a fully equipped compensated polarized microscope is unavailable.

Differentiating gout and calcium pyrophosphate deposition disease: Role of imaging

75-year-old Chinese lady with diabetes mellitus, hypertension and history of bilateral knee arthroplasty was diagnosed with gouty arthritis for 14 years

Patient-Reported Outcomes in Calcium Pyrophosphate Deposition Disease Compared to Gout and Osteoarthritis.

Calcium pyrophosphate deposition (CPPD) disease prevalence is similar to that of gout and osteoarthritis (OA), yet CPPD outcomes research greatly lags behind research in these other forms of arthritis. We compared validated patient-reported outcome measures in patients with CPPD vs gout and OA. Patients with CPPD were recruited from Brigham and Women's Hospital from 2018 to 2022. Presence of CPPD manifestations (acute calcium pyrophosphate [CPP] crystal arthritis, chronic CPP inflammatory arthritis, and/or OA with CPPD) was confirmed by medical record review. Baseline surveys included the Gout Assessment Questionnaire version 2.0, modified to ask about "pseudogout" rather than "gout"; Routine Assessment of Patient Index Data 3 (RAPID-3); and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We compared responses in patients with CPPD against published gout and OA cohort studies. Among 47 patients with CPPD, the mean age was 71.9 years and 51% were female. Sixty-eight percent had at least 1 episode of acute CPP crystal arthritis, 40% had chronic CPP inflammatory arthritis, and 62% had OA with CPPD. Pain visual analog scale scores during a flare were similar in CPPD (mean 6.8 [SD 1.9]) and gout (mean 6.7 [SD 2.6]; P = 0.78). Patients with CPPD reported significantly greater unmet treatment need than patients with gout (P = 0.04). RAPID-3 scores in CPPD (mean 8.1 [SD 5.6]) were lower than in gout (mean 12.1 [SD 6.2]; P < 0.01) and similar in OA (mean 6.8 [SD 6.1]; P = 0.30). Patients with CPPD had significantly worse WOMAC stiffness scores than patients with mild OA, and significantly better WOMAC function scores than patients with severe OA. Patients with CPPD may experience pain comparable to that in gout and OA and reported substantial unmet treatment needs.

CALCIUM PYROPHOSPHATE DIHYDRATE DEPOSITION DISEASE OF ELBOW WITH ULNAR NERVE NEUROPATHY: A CASE REPORT

Crystal deposition disorders are one of the causes of inflammatory arthropathy. A rare variety of this disorder is Calcium Pyrophosphate Dihydrate deposition disease. It is usually seen in the elderly and progresses as calcifications in and around the joint i.e. Chondrocalcinosis with repeated synovitis leading to degenerative changes of large and unusual or non-weight-bearing joints. It is a case report of 43 years housewife with a gradually enlarging mass at posteromedial aspect of the left elbow with ulnar nerve weakness for 1 year. Radiographs revealed degenerative joint with periarticular calcifications. The electrodiagnostic test showed ulnar nerve demyelination and axonal neuropathy. Surgical excision with decompression of ulnar nerve was done. Histopathology revealed features consistent with Pseudogout. Subsequent follow-up resulted in improvement of nerve function with no clinicoradiological evidence of recurrence. So, degenerative changes with periarticular calcifications in non-weight-bearing joints should be suspected for pseudogout. It may be associated with compressive neuropathy.

A single-centre retrospective case series of Anakinra for incident calcium pyrophosphate deposition disease.

In this 2-year retrospective case series, we characterise the calcium pyrophosphate deposition disease (CPPD) inpatient cohort at a single centre and assess the efficacy and safety of anakinra in its treatment. Adult inpatients with CPPD between 1st September 2020 and 30th September 2022 were identified by ICD-10 codes and confirmed based on clinical diagnosis and either CPP crystals on aspirate or chondrocalcinosis on imaging. Charts were reviewed for demographic, clinical, biochemical data, treatment choice, and response. Response to treatment was determined from chart documentation and calculated from time of first CPPD treatment. Daily responses to anakinra were recorded if anakinra was used. Seventy patients accounting for 79 cases of CPPD were identified. Twelve cases received anakinra, whilst 67 cases received conventional therapy only. Patient receiving anakinra were predominantly male, had multiple comorbidities, and had higher CRPs and serum creatinine when compared to the non-anakinra group. Anakinra was rapidly effective with the mean time to substantial and complete response being 1.7 and 3.6days respectively. Anakinra was well tolerated. This study adds to the small amount of retrospective data present about the use of anakinra in CPPD. We observed a rapid response to anakinra in our cohort with minimal adverse drug reactions. Key Points • Treatment of CPPD with anakinra appears to be rapidly efficacious without safety concerns.

Glucagon-Like Peptide 1 Receptor Agonists in Patients With Inflammatory Arthritis or Psoriasis: A Scoping Review.

Obesity is a proinflammatory state associated with increased disease severity in various types of inflammatory arthritis. Weight loss is associated with improved disease activity in certain forms of inflammatory arthritis such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We conducted a scoping review summarizing the literature evaluating the effect of glucagon-like peptide 1 (GLP-1) receptor agonists on weight and disease activity in patients with inflammatory arthritis or psoriasis. MEDLINE, PubMed, Scopus, and Embase were searched for publications evaluating the role of GLP-1 analogs in RA, PsA, psoriasis, axial spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, gout, and calcium pyrophosphate deposition disease. Nineteen studies were included: 1 gout study, 5 RA studies (3 basic science, 1 case report, and 1 longitudinal cohort), and 13 psoriasis studies (2 basic science, 4 case reports, 2 combined basic science/clinical studies, 3 longitudinal cohorts, and 2 randomized controlled trials). No psoriasis study reported on PsA outcomes. Basic science experiments demonstrated weight-independent immunomodulatory effects of GLP-1 analogs through inhibition of the NF-κB pathway (via AMP-activated protein kinase phosphorylation in psoriasis and prevention of IκBα phosphorylation in RA). In RA, improved disease activity was reported. In psoriasis, 4 of 5 clinical studies demonstrated significant improvements in Psoriasis Area Severity Index and weight/body mass index with no major adverse events. Common limitations included small sample sizes, short follow-up periods, and lack of control groups. GLP-1 analogs safely cause weight loss and have potential weight-independent anti-inflammatory effects. Their role as an adjunct in patients with inflammatory arthritis and obesity or diabetes is understudied, warranting future research.