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.

Bilateral Otic Manifestation of Pseudogout: A Unique Case Report of Conductive Hearing Loss.

Pseudogout is characterized by the deposition of calcium pyrophosphate dihydrate crystals (CPPD), primarily affecting large joints. Extra-articular manifestations, particularly in the head and neck region, are exceedingly rare. We report a unique case of bilateral isolated pseudogout of the middle ear manifesting with progressive conductive hearing loss as the first and only symptom of pseudogout. Otoscopy and CT scan often yield a differential diagnosis that includes tumors or cholesteatoma, necessitating surgery with histopathological examination. The definitive diagnosis is confirmed upon identification of calcium pyrophosphate dihydrate crystals. In most cases, removal of the crystals results in resolution of conductive hearing loss. Laryngoscope, 2024.

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.

Anakinra for Refractory Pseudogout in Patients with End-stage Renal Disease on Haemodialysis.

Calcium pyrophosphate deposition (CPPD) arthritis is the second most common type of crystal-induced arthritis after gout. Acute flares are commonly treated with non-steroidal anti-inflammatory drugs, intra-articular or short-term systemic glucocorticoids or colchicine. However, since there is no pharmacological treatment to reduce CPPD crystal burden, relapsing or chronic CPPD arthritis may be challenging to treat, particularly in patients with end-stage renal disease who are at risk for toxicity of the above medications. Since IL-1ß appears to be driving CPPD arthritis, we treated two patients with chronic CPPD arthritis and end-stage renal disease on haemodialysis with the IL-1ß receptor antagonist anakinra. In both patients, arthritis resolved quickly, while continuation of anakinra maintained remission and allowed complete glucocorticoid withdrawal. Therefore, anakinra may be a safe and effective option both for short and long-term treatment of CPPD arthritis in patients on chronic renal replacement therapy.

Acute cervical epidural abscess with concurrent calcium pyrophosphate deposition after cervical spinal surgery: A case report.

Background: Spinal epidural abscess (SEA) is a rare condition that may result in catastrophic outcomes. On the other hand, calcium pyrophosphate (CPP) deposition disease (CPPD) causes inflammatory arthritis. Spinal involvement of a crystal-induced inflammation caused by CPPD is also common. Surgery is a common risk factor for both SEA and CPPD; however, the postoperative acute onset of SEA complicated with CPPD is extremely rare. Case Description: A man in his 70s presented to our hospital, complaining of right upper limb weakness, loss of dexterity, and gait disturbance. The diagnosis of cervical spondylotic myelopathy was made, and he performed laminectomy at C3, C4, and C5 levels. Four days after the laminectomy, he suffered from acute neck pain, weakness, and hypoesthesia in his arms and legs. Magnetic resonance imaging revealed a mass occupying the dorsal epidural space of C6 and C7, compressing the cervical spinal cord. Considering the acute symptomatology, an acute spinal epidural hematoma after surgery was suspected; therefore, emergency C6 and C7 laminectomy was performed. Surgical findings indicated that the pressure inside the spinal canal was elevated, and the mass was purulent exudate. Pathological examination showed suppurative inflammation with concomitant deposition of CPP. SEA complicated with CPPD was considered; therefore, antibiotics and non-steroidal anti-inflammatory drugs were administered. The motor weakness and hypoesthesia were improved despite a slight residual deficit in his dexterity. Conclusion: An acute onset of SEA complicated with CPPD after cervical surgery has rarely been reported. The suppurative inflammation fostered by the crystal-induced inflammation may account for the acute symptomatology.

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.

Pseudogout mimicking cervical spine osteomyelitis and ventral epidural abscess: A case report and literature review.

Background: Calcium pyrophosphate deposition disease (CPPD), also known as "pseudogout," is a crystal deposition arthropathy involving the synovial and periarticular tissues. Pseudogout rarely presents in the axial spine. Here, we present the case of an 80-year-old female patient admitted after a mechanical fall, initially misdiagnosed on computed tomography (CT)/magnetic resonance studies with cervical osteodiscitis/ventral epidural abscess that proved to be pseudogout. Case Description: An 80-year-old female was admitted after a mechanical fall. The initial cervical CT scan showed multilevel degenerative changes with an acute C6 anterior wedge compression fracture, focal kyphosis, C5-6 disc space collapse, and endplate destruction. The magnetic resonance imaging showed marked contrast enhancement of the C5-6 vertebral bodies and disc space. An interventional radiology-guided biopsy of the C5-6 vertebral bodies and disc space was consistent with calcium pyrophosphate deposits, was diagnostic for pseudogout, and was negative for infection. She was managed conservatively with a rigid collar and seven days of oral prednisone. Conclusion: CPPD involvement in the axial spine is rare. Prompt pathologic diagnosis should be pursued to rule out an infectious process.

Calcified Chondroid Mesenchymal Neoplasms.

Calcified chondroid mesenchymal neoplasms (CCMN) represent a morphologic spectrum of related tumors. Historically, chondroid matrix or chondroblastoma-like features have been described in soft tissue chondroma, tenosynovial giant cell tumors (especially of the temporomandibular joint (TMJ) region), and in a subset of tophaceous pseudogout. Recently, these tumors have been found to share FN1-receptor tyrosine kinase (RTK) fusions. This review discusses the clinical, morphologic, immunohistochemical, and molecular genetic features of CCMN. The distinction from morphologic mimics is also discussed.

Calcium pyrophosphate crystal deposition with rotator cuff tear-A case report.

Calcium pyrophosphate dihydrate (CPPD) deposition disease is an inflammatory arthritis induced by calcium pyrophosphate (CPP) crystals and clinically it is called pseudogout. It usually deposits in articular cartilage and in periarticular soft tissues. But no cases of pseudogout in the rotator cuff without cartilage deposition or destruction have been reported so far. We present a case of a 57-year-old woman who was diagnosed as pseudogout with rotator cuff tear.

A Rare Case of Acute Calcium Pyrophosphate Deposition Disease Following Zoledronic Acid Infusion.

Calcium pyrophosphate deposition (CPPD) disease of the joints is a form of arthritis that can present in a severely debilitating form of pseudogout. Although mostly idiopathic, pseudogout has been reported following bisphosphonate therapy in only nine cases to date with a pathophysiology that remains unclear. We present the case of a 59-year-old postmenopausal woman who developed the rare onset of acute polyarticular CPPD disease following zoledronic acid infusion for the treatment of osteoporosis.

Non-loading versus loading low-dose colchicine in acute crystal-associated arthritis: A double-blinded randomized controlled study.

INTRODUCTION: This study aimed to compare the efficacy of non-loading versus loading low-dose colchicine in patients with acute crystal-associated arthritis. MATERIALS AND METHODS: All in-patients who were admitted to Chiang Mai University Hospital with non-arthritis disease and developed acute crystal-associated arthritis during admission (within 48 h after arthritis onset) were invited to join this study. The patients were randomized into two groups. Patients in Group I (non-loading group) and Group II (loading group) received colchicine at 1.2 and 2.4 mg in the first 24 h, respectively. The primary outcome was the patients' pain response at 24 h after treatment. RESULTS: Of 80 patients, 49 were acute gouty arthritis, and 31 acute calcium pyrophosphate (CPP) arthritis. The mean [95% CI] pain score was no different between Groups I and II at the baseline level (6.46[5.72-7.19] vs. 6.654[5.85-7.44], p = .867) and at 24 h (3.13[2.43-3.82] vs. 3.18[2.42-3.93], p = .907). The proportion of patients with ≥50% pain reduction was not different (57.50% vs. 55.00%, p = .822). Sensitivity analysis among patients with a baseline pain score of ≥4 showed the same pattern of response. Mild diarrhea was common and comparable in both groups. Subgroup analysis according to renal function (eGFR < 60 vs. ≥60 mL/min/1.73 m2 ) or type of crystals (acute gouty arthritis vs. acute CPP arthritis) also showed the same pattern of response. CONCLUSION: Non-loading low-dose colchicine was as effective as loading low-dose colchicine in patients with acute crystal-associated arthritis, regardless of renal function or type of crystals.

Orthostatic hypotension as an unusual presentation of spinal calcium pyrophosphate deposition disease: case report and review of literature.

Calcium pyrophosphate crystal deposition disease (CPPD), also known as pseudogout, with spinal involvement, is associated with clinical manifestations of acute nerve compression or chronic spinal stenosis. Precipitation of crystals of calcium pyrophosphate dihydrate in connective tissues can lead to acute inflammatory arthritis, degenerative chronic arthropathies, and radiographic evidence of cartilage calcification. We present a case of an 87-year-old woman, with unstudied chronic polyarthralgia and symptomatic orthostatic hypotension. It were documented acute calcium pyrophosphate deposition wrist arthritis, and cervical CT and MRI was suggestive of spinal involvement of CPPD. Workup excluded other causes of OH. Surgical approach could be indicated to minimize the symptoms, but it was contra-indicated due to the patient's performance status, so histological diagnosis was not possible. Muscle atrophy played an important part in the rapid progression of this insidious chronic disease. Conservative and symptomatic treatment achieve scarce short-term clinical improvement. Spinal involvement of CPPD was thought to be rare but recent studies show a higher prevalence than expected. We call for attention to the extent of structural changes that may occur when not early diagnosed nor treated. High clinical suspicion is required and this is, to our knowledge, the first report of orthostatic hypotension as a presentation of CPPD.

A case of pseudogout attack after zoledronic acid treatment in primary hyperparathyroidism.

Pseudogout (PG) is an inflammatory arthropathy that develops due to the accumulation of calcium pyrophosphate dihydrate crystals in synovial structures. Herein, we present a 59-year-old male patient with PG developed as a result of zoledronic acid (ZA) infusion, which was administered due to primary hyperparathyroidism. The patient with parathyroid adenoma was given ZA since the calcium level did not decrease despite intravenous saline and loop diuretic. One day after ZA administration, the patient had severe pain, fever, and swelling in joints. The radiograph showed chondrocalcinosis. Calcium pyrophosphate deposition were observed in the arthrocentesis fluid under polarized light. The patient's symptoms regressed after anakinra and colchicine treatment. To the best of our knowledge, this is the first case report of a PG attack after ZA treatment for primary hyperparathyroidism. Additionally, there have been few cases of PG after bisphosphonate treatment for osteoporosis in the literature, signifying that more care should be taken when administering bisphosphonate therapy in patients with risk factors.

Acute Inflammatory Arthropathy and Hypercalcemia Leading to a Diagnosis of Primary Hyperparathyroidism in a Patient With Known Sarcoidosis.

Calcium pyrophosphate deposition disease (CPPD) is a crystal-induced arthropathy characterized by calcium pyrophosphate crystal deposition in joints and soft tissues. The diagnosis is suggested by the presence of chondrocalcinosis on x-ray but is most often diagnosed by synovial fluid analysis (SFA). CPPD is associated with aging and metabolic disorders such as hyperparathyroidism. In this case, we present an 87-year-old woman with known sarcoidosis who presented with acute arthropathy, hypercalcemia, and radiographic evidence of CPPD. Her hypercalcemia had been attributed to her sarcoidosis in the past without a full workup. Hypercalcemia in the setting of suspected CPPD led to a full workup for hypercalcemia and ultimately led to a diagnosis of primary hyperparathyroidism. This case highlights the importance of a complete evaluation for hypercalcemia in the setting of CPPD, even when another disease, such as sarcoidosis, could explain hypercalcemia. Ultimately, CPPD aided in diagnosing hyperparathyroidism in our patient with known sarcoidosis.

A Case of Tophaceous Pseudogout with Destruction of the Skull Base at the Temporomandibular Joint.

We report a case of tophaceous pseudogout that occurred in the temporomandibular joint (TMJ) and presented with skull base destruction. The patient was a 73-year-old woman, who complained of an obstructed ear sensation in December 2021. The otolaryngological examination was unremarkeable, and a computed tomography scan revealed a calcified lesion in the left TMJ. Suspected of having osteochondroma, the patient was brought to our hospital. She was performed tumor resection as much as possible under general anesthesia revealed nodular pseudogout. The patient refused to undergo total resection due to the necessary craniotomy and the risk of postoperative complications. Instead, the patient decided to undergo following-up. One year and 4 months have passed since the biopsy operation, but there is no tendency to re-increase.

An Update on the Diagnosis and Management of Calcium Crystal Disease.

PURPOSE OF REVIEW: This article aims to review the challenges to diagnosis and management of calcium crystal deposition diseases and evaluate the literature published over the past 3 years. RECENT FINDINGS: The awaited development of classification criteria is an essential step in the progression of calcium crystal deposition disease clinical research. There have been recent improvements in the accuracy of imaging for the diagnosis of crystal deposition diseases with published definitions of characteristic features. Factors associated with acute flares of disease have been identified and an association with increased cardiovascular risk has been demonstrated. Targeted treatment options for calcium crystal diseases remain elusive. However, there have been advances in understanding the molecular mechanisms of disease revealing potential targets for future drug development. Calcium-crystal deposition diseases are increasing in incidence and prevalence as populations age and continue to associate with a high burden of disability. Despite this, calcium crystal deposition disease remains under-studied with a paucity of evidence-based treatment guidelines.

Differences in the Optical Response of MSU and CPP Crystals During Magnetic Orientation: Possibility of Diagnosing Gout and Pseudogout.

Pseudogout is crystalline arthritis. It has a similar clinical picture to that of gout, and it is difficult to distinguish the two diseases using conventional analysis methods. However, it is important to identify the different crystals responsible for these two cases because the treatment strategies are different. In a previous study, we reported magnetic orientation of monosodium urate (MSU) crystals, which are the causative agent of gout, at the permanent magnet level. In this study, we investigated the effect of an applied magnetic field on calcium pyrophosphate (CPP) crystals, which are the causative agent of pseudogout, and the difference in the magnetic responses of CPP and MSU crystals. We found that the CPP crystals were oriented in a magnetic field on milli-Tesla order because of the anisotropy of the diamagnetic susceptibility. In addition, the CPP crystals exhibited different anisotropic magnetic properties from those of MSU crystals, which led to a characteristic difference between the orientations of the two crystals. That is, we found that the causative agents of gout and pseudogout responded differently to a magnetic field. This report suggests that the discrimination between CPP and MSU by optical measurements is possible by application of magnetic fields appropriately. © 2023 Bioelectromagnetics Society.