Efficacy of a single ultrasound-guided injection of high molecular weight hyaluronic acid combined with collagen tripeptide in patients with knee osteoarthritis and chondrocalcinosis.

Introduction: Osteoarthritis (OA) and calcium pyrophosphate deposition (CPPD) often co-exist, this resulting in a clinical condition characterized by amplified inflammation and more severe and faster cartilage degeneration compared to OA alone. Our study aims to explore the efficacy of a therapeutic approach that addresses both conditions, using a combination of a high molecular weight hyaluronic acid (HMWHA) and collagen tripeptide (CTP). Additionally, safety profile and baseline characteristic predictive value were evaluated. Methods: We conducted a retrospective study on patients diagnosed with symptomatic knee OA (KOA) and CPPD treated by ultrasound (US) guided intraarticular injections of HMWHA-CT in the outpatient clinics of the Interdisciplinary Pain Medicine Unit at Santa Maria Maddalena Hospital, Occhiobello, Italy and in the Rheumatology Unit of the Emergency County Hospital Craiova, Romania (ECH Craiova). All the patients underwent clinical and US evaluation at baseline, 1, 3, and 6 months. From clinical point of view, Numeric Rating Scale (NRS) pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were recorded. US data included detection of synovitis, cartilage damage, osteophytes, and CPPD deposits. Clinical efficacy was defined with NRS and WOMAC variations in respect to baseline and using the minimal clinically important difference values: an improvement of 2 point for NRS pain and 10 for the total score for WOMAC. Results: Twenty-nine patients (34 knees) were injected and evaluated. Overall pain levels, as measured by NRS, demonstrated a consistent decrease in patients across all follow-up intervals, with the most substantial improvement at the 6-month compared to baseline measurements. A significative proportion of patients achieved the minimum clinically detectable improvement, specifically 79% for NRS and 83% for WOMAC (19 and 20 patients, respectively). Conclusion: Our data showed a significant efficacy of ultrasound guided HMWHA-CT, in patients with KOA and CPPD, thus making it reasonable to consider that the combination of HMWHA and CTP can provide a strong anti-inflammatory effect.

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

PURPOSE OF THE REVIEW: This review provides an overview of medical conditions and risk factors associated with CPPD. RECENT FINDINGS: 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.

Calcium Pyrophosphate Crystal Formation and Deposition: Where Do we Stand and What Does the Future hold?

PURPOSE OF THE REVIEW: Although calcium pyrophosphate deposition (CPPD) has been known since the 1960s, our understanding of its pathogenesis remains rudimentary. This review aims to illustrate the known mechanisms underlying calcium pyrophosphate (CPP) crystal formation and deposition and explore future directions in research. By examining various perspectives, from basic research to clinical and imaging assessments, as well as new emerging methodologies, we can establish a starting point for a deeper understanding of CPPD pathogenesis. RECENT FINDINGS: Recent years have seen significant advances in CPPD research, particularly in the clinical field with the development of the 2023 ACR/EULAR classification criteria for CPPD disease, and in imaging with the introduction of the OMERACT ultrasonographic definitions and scoring system. However, progress in basic research has been slower. New laboratory approaches, such as Raman spectroscopy and omics sciences, offer promising insights that may help piece together the puzzle of CPPD. CPPD is a common yet understudied condition. As the population ages and CPPD becomes more prevalent, there is an urgent need to better understand the disease and the mechanisms involved in crystal formation and deposition, in order to improve diagnosis and therapeutic approaches.

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.

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.

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

OBJECTIVE: Recent 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. METHODS: We 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. RESULTS: A 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). CONCLUSION: ACS 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.

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.

Cauda Equina Syndrome Caused by Pseudogout Involving the Lumbar Intervertebral Disc

Calcium pyrophosphate dihydrate (CPPD) deposition disease, also known as pseudogout, is a disease that causes inflammatory arthropathy in peripheral joints, however, symptomatic involvement of the intervertebral disc is uncommon. Herein, we describe a 59-yr-old patient who presented with cauda equina syndrome. Magnetic resonance imaging of the patient showed an epidural mass-like lesion at the disc space of L4-L5, which was compressing the thecal sac. Biopsy of the intervertebral disc and epidural mass-like lesion was determined to be CPPD deposits. We reviewed previously reported cases of pseudogout involving the lumbar intervertebral disc and discuss the pathogenesis and treatment of the disease.

Idiopathic Calcium Pyrophosphate Dihydrate (CPPD) Crystal Deposition Disease in a Young Female Patient : A Case Report

PURPOSE: Calcium pyrophosphate dihydrate crystal deposition disease(CPPD) is a disease of the elderly and extremely rare in young individuals. If young people develop CPPD crystal deposition disease, it may be associated with metabolic diseases, such as hemochromatosis, hyperparathyroidism, hypophosphatasia, hypomagnesemia, Wilson's disease, hypothyroidism, and gout. MATERIALS AND METHODS: Therefore, in young-onset CPPD crystal deposition disease, an investigation of any predisposing metabolic conditions is warranted. CONCLUSION: We report a case of a young female patient who presented with idiopathic CPPD crystal deposition disease at 25 years of age.

Idiopathic Calcium Pyrophosphate Dihydrate (CPPD) Crystal Deposition Disease in a Young Male Patient: A Case Report

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is a disease of the elderly and extremely rare in young individuals. If young people develop CPPD crystal deposition disease, it may be associated with metabolic diseases such as hemochromatosis, hyperparathyroidism, hypophosphatasia, hypomagnesemia, Wilson's disease, hypothyroidism, gout, acromegaly, and X-linked hypophosphatemic rickets. Therefore, in young-onset polyarticular CPPD crystal deposition disease, investigation for predisposing metabolic conditions is warranted. We report a case of a young male patient with idiopathic CPPD crystal deposition disease, who did not have any evidences of metabolic diseases after thorough evaluations. As far as we know, this is the first report of a young male patient presented with idiopathic CPPD crystal deposition disease.

A Case of Calcium Pyrophosphate Dihydrate Crystal Deposition Disease Associated with Gout / 대한류마티스학회지

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease has various patterns of clinical manifestation ranging from an absence of symptoms to a severely destructive arthropathy. A number of metabolic diseases and physiologic stresses, such as aging and trauma, have been associated with CPPD crystal deposition. The coexistence of CPPD crystal deposition disease and gout varies from 2 to 8%. The mechanism of this association has been postulated to be a predisposition to the local deposition of pyrophosphate due to the presence of urate crystal, perhaps acting as a nucleating agent or factor which predispose to the deposition of both kinds of crystals. In Korea, although it is considered that CPPD crystal deposition occasionally coincides monosodium urate crystal, it has not been reported so far. We report a case with CPPD crystal deposition disease combined with gout in a patient who has suffered from osteoarthritis, which is diagnosed by polarized microscopic examination of synovial fluid.

Calcium Pyrophosphate Dihydrate (CPPD)Crystal Deposition Disease Mimicking Meningitis:A case Report and Review of the Literature / 대한류마티스학회지

Calcium pyrophosphate dihydrate (CPPD)crystal deposition disease is one of the most common causes of arthralgia in elderly.The acute form (pseudogout) may present as acute monoarticular or polyarticular arthritis.It is often accompanied by high fever and sometimes simulates acute infectious condition.The knee is the joint most frequently affected by pseudogout but other sites such as wrist,shoulder,ankle,elbow and hands may be affected.A few cases involving cervical and lumbar spine mistaken for CNS infection have also been described in foreign countries.We report here a case of CPPD crystal deposition disease mimicking meningitis.