Selective Dissolution of Calcium Pyrophosphate Dihydrate Crystals Using a Pyrophosphate Specific Receptor.

Pseudo-gout is caused by the deposition of highly insoluble calcium pyrophosphate dihydrate (CPPD) crystals in the joints of sufferers. This leads to inflammation and ultimately joint damage. The insolubility of CPPD is driven by the strong attraction of di-cationic calcium ions with tetra-anionic pyrophosphate ions. One of the challenges of dissolving CPPD is that a related mineral, hydroxy apatite (HA) is present in larger amounts in the form of bone and also contains strongly interacting calcium and phosphate ions. Our aim in this work was to selectively dissolve CPPD in preference to HA. To accomplish this, we used a known receptor for pyrophosphate that contains two complexed zinc ions that are ideally spaced to interact with the tetra-anion of pyrophosphate. We hypothesized that such a molecule could act as a preorganized tetra-cation that would be able to outcompete the two calcium ions present in the crystal lattice of CPPD. We demonstrate both visually and through analysis of released phosphorous that this molecule is able to preferentially dissolve CPPD over the closely related HA and thus can form the basis for a possible approach for the treatment of pseudo-gout.

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 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.

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.

Identification of Common Pathogenic Pathways Involved in Hemochromatosis Arthritis and Calcium Pyrophosphate Deposition Disease: a Review.

OBJECTIVES: Arthritis is a common clinical manifestation of hereditary hemochromatosis (HH), and HH is one of a handful of conditions linked to calcium pyrophosphate deposition (CPPD) in joints. The connection between these two types of arthritis has not yet been fully elucidated. In light of new pathogenic pathways recently implicated in CPPD involving bone, we reviewed the literature on the etiology of hemochromatosis arthropathy (HHA) seeking shared pathogenic mechanisms. RESULTS: Clinical observations reinforce striking similarities between HHA and CPPD even in the absence of CPP crystals. They share a similar joint distribution, low grade synovial inflammation, and generalized bone loss. Excess iron damages chondrocytes and bone cells in vitro. While direct effects of iron on cartilage are not consistently seen in animal models of HH, there is decreased osteoblast alkaline phosphatase activity, and increased osteoclastogenesis. These abnormalities are also seen in CPPD. Joint repair processes may also be impaired in both CPPD and HHA. CONCLUSIONS: Possible shared pathogenic pathways relate more to bone and abnormal damage/repair mechanisms than direct damage to articular cartilage. While additional work is necessary to fully understand the pathogenesis of arthritis in HH and to firmly establish causal links with CPPD, this review provides some plausible hypotheses explaining the overlap of these two forms of arthritis.

Management of temporomandibular joint diseases: a rare case report of coexisting calcium pyrophosphate crystal deposition and synovial chondromatosis.

BACKGROUND: The coexistence of calcium pyrophosphate dihydrate crystal deposition (CPP) and synovial chondromatosis (SC) in the temporomandibular joint (TMJ) is rarely reported. CPP disease (CPPD) is complex arthritis synonymous with excessive pyrophosphate production and variable aberrations in mineral and organic phase metabolism of the joint cartilage, leading to local inundated CPP and crystal deposition of partially deciphered predispositions. Meanwhile, SC is a rare benign synovial joint proliferative disease of unclear etiology and has a low risk of malignant transformation. However, SC manifests severe joint disability and dysfunction because of connective tissue metaplasia of the synovial membrane, which forms cartilaginous nodules with or without calcifications or ossifications. These nodules often detach and form intra-articular loose bodies and very rarely within extraarticular spaces. CASE PRESENTATION: We report the case of a 61-year-old man to expand the body of literature on these unusual coexisting arthropathies of the TMJ. The patient presented to our hospital in 2020 with complaints of pain in the right TMJ and trismus for over 6 months. Radiographic assessments of the TMJ provided a preoperative provisional diagnosis of SC. However, the histopathology of the open biopsy revealed tumor-like lesions comprising several deposits of rhomboid and rod-shaped crystals that displayed positive birefringence in polarized light, confirming a coexistence of CPPD. A second-stage operation was performed for the complete removal of the loose bodies and chalk-like lesions including synovectomy. No evidence of recurrence was recorded after a follow-up of nearly 1.5 years. CONCLUSIONS: Isolated CPPD and SC of the TMJ are prevalent in the literature however, monoarticular coexistence of these diseases is rare, due to the lack of consistency in the diagnostic criteria in clinical practice. Moreover, optimal treatment depends on several considerations. This report delineated the molecular etiopathology and underscored the need for continued deciphering of the causal mechanisms of coexisting CPPD and SC of the TMJ. In addition, the importance of confirmatory testing for accurate diagnosis, and appropriate management of these diseases were discussed.

Multifocal calcific periarthritis with distinctive clinical and radiological features in patients with CD73 deficiency.

OBJECTIVES: Arterial calcification due to deficiency of CD73 (ACDC) is a hereditary autosomal recessive ectopic mineralization syndrome caused by loss-of-function mutations in the ecto-5'-nucleotidase gene. Periarticular calcification has been reported but the clinical characterization of arthritis as well as the microstructure and chemical composition of periarticular calcifications and SF crystals has not been systematically investigated. METHODS: Eight ACDC patients underwent extensive rheumatological and radiological evaluation over a period of 11 years. Periarticular and synovial biopsies were obtained from four patients. Characterization of crystal composition was evaluated by compensated polarized light microscopy, Alizarin Red staining for synovial fluid along with X-ray diffraction and X-ray micro tomosynthesis scanner for periarticular calcification. RESULTS: Arthritis in ACDC patients has a clinical presentation of mixed erosive-degenerative joint changes with a median onset of articular symptoms at 17 years of age and progresses over time to the development of fixed deformities and functional limitations of small peripheral joints with, eventually, larger joint and distinct axial involvement later in life. We have identified calcium pyrophosphate and calcium hydroxyapatite (CHA) crystals in SF specimens and determined that CHA crystals are the principal component of periarticular calcifications. CONCLUSION: This is the largest study in ACDC patients to describe erosive peripheral arthropathy and axial enthesopathic calcifications over a period of 11 years and the first to identify the composition of periarticular calcifications and SF crystals. ACDC should be considered among the genetic causes of early-onset OA, as musculoskeletal disease signs may often precede vascular symptoms.

Neutrophil extracellular traps release in gout and pseudogout depends on the number of crystals regardless of leukocyte count.

OBJECTIVES: Microcrystal-induced arthritis is still an unresolved paradigm for medicine. Overt inflammation may be absent even when crystals occur in SF. Recently, the production of neutrophil extracellular traps (NETs) embedding MSU crystals has been proposed as a possible mechanism of the auto-resolution of the inflammatory phase during gout. We aimed to verify and quantify the release of NETs in SFs during gout and pseudogout attacks and to compare any differences with respect to crystals and neutrophils number, and to analyse activation of necroptosis pathway in SF from crystal-induced arthritis. METHODS: SF samples were obtained by arthrocentesis from 22 patients presenting acute crystal-induced arthritis, gout or pseudogout (n = 11 each group), and from 10 patients with acute non-crystal arthritis as controls. NETosis was quantified in SF by nucleic acid stain and by quantification of human neutrophil elastase. Activation of phosphorylated MLKL was assessed by western blot. RESULTS: We observed that SF neutrophils encountering MSU and CPPD crystals during episodes of gout and pseudogout release NETs in relation to the number of crystals in SF and irrespective of neutrophil density and type of crystal. This release was accompanied by necroptosis through the activation of the MLKL pathway. CONCLUSIONS: Our findings suggest that a role of NETs in crystal-induced arthritis is to 'trap extracellular particles', including microcrystals. Embedding crystals in aggregates of NETs may be the basis of tophi and CPPD deposition, and may have implications for disease evolution rather than for spontaneous resolution of the acute attack.

The role of Interleukin-1 receptor antagonist as a treatment option in calcium pyrophosphate crystal deposition disease.

Calcium Pyrophosphate Crystal Deposition (CPPD) disease is characterized by the deposition of calcium pyrophosphate crystals in the cartilage. In most cases, it can manifest as a subclinical condition named chondrocalcinosis, often revealed by joint x-ray examination. In other cases, deposition can cause flares of arthritis, known as acute CPP crystal arthritis. In the last few years, many pathogenic pathways have been discovered. Interleukin-1 (IL-1) plays a key role in the pathogenesis of CPPD disease, both as a mediator of inflammatory response to crystals and as a promoter of damage to articular cartilage. In this review, we investigated the role of IL-1R inhibitor, such as Anakinra, as an alternative to the various therapeutic strategies for CPPD disease, especially among patients resistant to traditional treatment with NSAIDs, corticosteroids and colchicine.

Rare presentation of intradural calcium pyrophosphate dihydrate crystal deposition.

Calcium pyrophosphate dihydrate crystal deposition (CPPD), also known as pseudogout, can have spinal manifestations in roughly one quarter of patients. We present a rare, intradural manifestation of CPPD requiring surgical intervention, with a review of pertinent differential diagnoses on imaging. A 48-year-old male presented with urinary retention, and was found to have an intradural lesion with peripheral enhancement on gadolinium T1-weighted magnetic resonance imaging. Due to the patient's progressive neurological deterioration, he was taken for a minimally invasive approach for resection of the lesion. Histopathological analysis revealed crystal deposits with rhomboidal birefringence consistent with CPPD. The imaging features of this lesion were atypical for any of the traditional intradural extramedullary lesions. Typically seen extradurally, recognizing CPPD as a potential culprit for intradural compression is helpful to recognize for providers.

Tacrolimus induced pseudogout following allogeneic hematopoietic cell transplant.

INTRODUCTION: Crystalline arthritis (CA), characterized by acute joint pain and erythema secondary to calcium pyrophosphate deposition (CPPD, or pseudogout) or monosodium urate crystals (gout), is a potentially underreported complication following allogeneic hematopoietic cell transplant (alloHCT). Graft-versus-host disease prophylaxis with calcineurin inhibitors (CNIs) causes hypomagnesemia and hyperuricemia, resulting in CA. CA related to tacrolimus has yet to be characterized following alloHCT. CASE REPORT: We retrospectively reviewed records of 450 consecutive patients undergoing alloHCT and identified 15 (3.3% incidence) who developed CA on tacrolimus. Large joints were involved in 10 (66.7%) patients, all patients had recent hypomagnesemia, and no patient had hyperuricemia, suggesting CPPD was the most likely etiology.Management and outcome: Eleven (73.3%) patients received systemic corticosteroids; 6 as initial therapy and 5 added to or substituted for colchicine in the setting of slow or inadequate response. The median duration of corticosteroid therapy was 6 days, however 2 patients (13.3%) required prolonged maintenance due to recurrence. Eleven (73.3%) patients received colchicine; 9 as initial therapy and 2 added to or substituted for corticosteroids in the setting of slow or inadequate response. The median duration of colchicine therapy was 18 days. The median time to symptom resolution was 21 days. DISCUSSION: Patients on tacrolimus following alloHCT presenting with acute joint pain and erythema should be evaluated for CPPD. Hypomagnesemia secondary to CNIs is likely the precipitating factor for CPPD in this population. Patients can effectively be managed with systemic corticosteroids and/or colchicine, however prolonged duration of treatment and even maintenance may be necessary. Based on the Naranjo Algorithm, CPPD secondary to tacrolimus induced hypomagnesemia is a possible adverse drug event, with a score of 3-4.

A Phage Display-Identified Short Peptide Capable of Hydrolyzing Calcium Pyrophosphate Crystals-The Etiological Factor of Chondrocalcinosis.

Chondrocalcinosis is a metabolic disease caused by the presence of calcium pyrophosphate dihydrate crystals in the synovial fluid. The goal of our endeavor was to find out whether short peptides could be used as a dissolving factor for such crystals. In order to identify peptides able to dissolve crystals of calcium pyrophosphate, we screened through a random library of peptides using a phage display. The first screening was designed to select phages able to bind the acidic part of alendronic acid (pyrophosphate analog). The second was a catalytic assay in the presence of crystals. The best-performing peptides were subsequently chemically synthesized and rechecked for catalytic properties. One peptide, named R25, turned out to possess some hydrolytic activity toward crystals. Its catalysis is Mg2+-dependent and also works against soluble species of pyrophosphate.

Fluorescence Differentiation of ATP-related Multiple Enzymatic Activities in Synovial Fluid as a Marker of Calcium Pyrophosphate Deposition Disease using Kyoto Green.

Calcium pyrophosphate deposition disease (CPPD) is a crystal induced inflammation in joints, and causes severe pain in elderly people. The accumulation of pyrophosphate (PPi) in synovial fluid (SF) results from several enzymatic reactions, especially the highly activated e-NPPs, which catalyze the conversion of ATP to PPi. This study demonstrates the detection of relative catalytic activity of 3 enzymes-ecto-nucleotide pyrophosphatase/phosphodiesterases (e-NPPs), tissue nonspecific alkaline phosphatase (TNAP), and ecto-nucleoside triphosphate diphosphohydrolases (e-NTPDases)-using a single molecular sensor called Kyoto Green. Kyoto Green exhibits excellent performance in sensing the catalytic activity of the commercial representatives of the e-NPPs, TNAP, and e-NTPDases, which are ENPP1, PPase, and apyrase, respectively, in both single-enzyme and multi-enzyme assays. Analysis of SF enzymes in 19 SF samples from human and swine revealed moderate activity of e-NPPs, high activity of e-NTPDases, and low activity of TNAP. Our newly developed method for analysis of multiple enzymatic activities using Kyoto Green in biological SF will assist improvement in accuracy of the CPPD prognosis/diagnosis, which will minimize unnecessary medical procedures.

Calprotectin discriminates septic arthritis from pseudogout and rheumatoid arthritis.

OBJECTIVE: We aimed to determine whether calprotectin and α-defensins could discriminate septic from other inflammatory arthritides. METHODS: Synovial fluids with a predominance of neutrophils from patients with septic arthritis, pseudogout and RA were prospectively collected. Neutrophil-related proteins calprotectin and human neutrophil α-defensins levels were assessed in synovial fluids. Demographic parameters and biomarkers with P-value ⩽0.05 for differentiating septic from non-septic arthritis were included in a multivariable model. Multivariable logistic regression with stepwise selection was performed to build the final combined model. RESULTS: A total of 74 patients were included: septic arthritis (n = 26), pseudogout (n = 28) and RA (n = 20). Patients with septic arthritis were more likely to be male and young, and to display higher synovial neutrophil count. Calprotectin was significantly increased in patients with septic arthritis. The multivariable model included calprotectin, synovial fluid neutrophil count and gender. Calprotectin was the only biomarker that discriminated septic arthritis from non-septic inflammatory arthritides, with 76% sensitivity, 94% specificity and a positive likelihood ratio = 12.2 at the threshold for calprotectin of 150 mg/l. CONCLUSION: Synovial fluid calprotectin is a relevant biomarker to discriminate septic arthritis from other inflammatory arthritides. This biomarker should be tested in an independent cohort.

Issues in CPPD Nomenclature and Classification.

PURPOSE OF REVIEW: This paper covers confusion and challenges in the nomenclature of calcium pyrophosphate deposition disease. Clinicians, investigators, and patients are faced with a variety of terms that are used to describe CPPD and its phenotypes, and clarity is greatly needed to help advance research and patient care. Motivation for the upcoming development of CPPD classification criteria is reviewed. RECENT FINDINGS: EULAR proposed recommended terminology for CPPD in 2011. International Classification of Diseases (ICD-9 and ICD-10) billing codes identify definite or probable CPPD with variable accuracy depending on the clinical setting and comparator group. READ diagnostic codes have been employed to identify pseudogout in UK datasets but their accuracy has not been evaluated. CPPD classification criteria will provide a system for identifying a relatively homogenous group of patients to be included in clinical studies, enabling comparison of outcomes across studies. CPPD nomenclature remains challenging for clinicians, investigators, and patients. A lay-friendly definition of CPPD, using easily accessible terminology, would be welcome. CPPD classification criteria are a necessary step in moving forward CPPD clinical research and may involve a range of clinical, laboratory, and imaging modalities.

Effects of low-level laser therapy on the organization of articular cartilage in an experimental microcrystalline arthritis model.

The aim of this study was to evaluate the effects of low-level laser therapy using the gallium arsenide laser (λ = 830 nm) on the articular cartilage (AC) organization from knee joint in an experimental model of microcrystalline arthritis in adult male Wistar rats. Seventy-two animals were divided into three groups: A (control), B (induced arthritis), and C (induced arthritis + laser therapy). The arthritis was induced in the right knee using 2 mg of Na4P2O7 in 0.5 mL of saline solution. The treatments were daily applied in the patellar region of the right knee after 48 h of induction. On the 7th, 14th, and 21st days of treatment, the animals were euthanized and their right knees were removed and processed for structural and biochemical analysis of the AC. The chondrocytes positively labeled for the TUNEL reaction were lower in C than in B on the 14th and 21st days. The content of glycosaminoglycans and hydroxyproline in A and C was higher than B on the 21st day. The amount of tibial TNF-α in B and C was lower than in A. The amount of tibial BMP-7 in B and C was higher than in A. The femoral MMP-13 was lower in B and C than for A. The tibial TGF-ß for C was higher than the others. The femoral ADAMT-S4 content of A and C presented similar and inferior data to B on the 21st day. The AsGa-830 nm therapy preserved the content of glycosaminoglycans, reduced the cellular changes and the inflammatory process compared to the untreated group.

Acute arthritis: predictive factors and current practice in the approach to diagnosis and management across two hospitals in Sydney.

BACKGROUND: Literature pertaining to the predictive factors for septic arthritis is limited. AIMS: The primary objective was to investigate the predictive factors for septic arthritis. The secondary objectives were to investigate the predictive factors for crystal arthritis and to explore current practices in the management of acute arthritis. METHODS: A retrospective analysis was undertaken. All patients with an acute arthritis who underwent a joint aspiration for diagnostic and management purposes were considered for inclusion. The outcome measures were patient demographics, findings on physical examination, findings on blood and synovial fluid analysis and management. RESULTS: Of the patients who presented with an acute arthritis, 24 of the 172 joint aspirations undertaken were positive for bacteria (13.95%). Of the 172 joint aspirations, 90 were positive for crystals (52.33%). Investigated variables associated with increased risk for the presence of bacteria on synovial fluid included features of sepsis (P < 0.001), joint-restricted range of motion (P = 0.048), elevated C-reactive protein (P < 0.001) and elevated total leukocyte count on synovial fluid (P < 0.001). Of the 24 joint aspirations that were positive for bacteria, 13 had associated positive blood cultures (54.17%). Of the 172 joint aspirations, antibiotics were administered in 96 cases (55.81%). Of these, antibiotics were administered prior to joint aspiration in 41 cases (42.71%). CONCLUSIONS: In our study, the most common cause of acute arthritis was crystal arthropathy. An accurate physical examination in conjunction with synovial fluid analysis is of particular importance in diagnosing septic arthritis. Blood cultures are not a reliable substitute for joint aspiration but should nevertheless be undertaken.

Pseudogout among Patients Fulfilling a Billing Code Algorithm for Calcium Pyrophosphate Deposition Disease.

To test the performance of a billing claims-based calcium pyrophosphate deposition disease (CPPD) algorithm for identifying pseudogout. We applied a published CPPD algorithm at an academic institution and randomly selected 100 patients for electronic medical record review for 3 phenotypes: (1) definite/probable CPPD, (2) definite/probable pseudogout; (3) definite pseudogout. Clinical data were recorded and positive predictive value (PPV) (95% CI) for each phenotype was calculated. We then modified the published algorithm to require ≥ 1 of 4 relevant terms ("pseudogout", "calcium pyrophosphate crystals", "CPPD", or "chondrocalcinosis") through automated text searching in clinical notes, and re-calculated PPVs. To estimate the percentage of pseudogout patients not identified by the published algorithm, we reviewed a random sample of 50 patients with ≥ 1 of 4 relevant terms in clinical notes who did not fulfill the published algorithm. Among patients fulfilling the published algorithm, 68% had ≥ 1 of 3 phenotypes. The published algorithm had PPV 24.0% (95% CI 19.3-28.7%) for definite/probable pseudogout and 18.0% (95% CI 14.5-21.5%) for definite pseudogout. Requiring ≥ 1 of 4 relevant terms in clinical notes increased PPV to 33.3% (95% CI 26.8-39.8%) for definite/probable pseudogout and 24.6% (95% CI 19.8-29.4%) for definite pseudogout. Among patients not fulfilling the published algorithm, 16.0% had definite/probable pseudogout and 6.0% had definite pseudogout. A billing code-based CPPD algorithm had low PPV for identifying pseudogout. Adding text searching modestly enhanced the PPV, though it remained low. These findings highlight the need for improved approaches to identify pseudogout to facilitate epidemiologic studies.

An investigation of the independent risk factors that differentiate gout from pseudogout in patients with crystal-induced acute arthritis: a cross-sectional study.

OBJECTIVES: To identify independent risk factors that differentiate gout from pseudogout in patients that present with crystal-induced acute arthritis. METHODS: This cross-sectional study was conducted at Siriraj Hospital (Bangkok, Thailand) during the 25 May 2014-28 November 2014 study period. Patients who presented with crystal-induced acute arthritis were eligible for inclusion. Diagnosis of gout or pseudogout was made by microscopic visualization and analysis of crystals in synovial fluid. Patients with other causes of acute arthritis were excluded. Patients diagnosed with gout were compared with patients diagnosed with pseudogout and factors with a p value less than 0.05 were included in logistic regression analysis. RESULTS: A total of 103 patients were included. Gout and pseudogout were established in 59 (56.7%) and 44 (42.3%) patients, respectively. Gout patients were younger than pseudogout patients (66.9 ± 14.5 vs. 78.9 ± 12.0 years; p = 0.0001); had higher BMI (22.9 ± 2.5 vs. 21.0 ± 2.5 kg/m2; p = 0.001); had history of recurrent arthritis (91.5 vs. 9.1%; p = 0.001); had higher prevalence of below-knee arthritis (66.1 vs. 31.8%; p = 0.001); had less periarticular soft tissue swelling (57.6 vs. 81.8%; p = 0.01); and had hyperuricemia (8.0 ± 2.5 vs. 5.6 ± 2.7; p = 0.001). In adjusted multivariate analysis, hyperuricemia during acute arthritis/gouty attack characterized gout (OR 2.08, 95% CI 1.2-3.6), while monoarticular attack (OR 4.12, 95% CI 1.3-13.0) and periarticular soft tissue swelling (OR 4.03, 95% CI 1.1-14.9) were indications for pseudogout. CONCLUSIONS: The independent risk factors were found to differentiate gout from pseudogout: Gout: hyperuricemia during gouty attack; Pseudogout: monoarticular attack and periarticular soft tissue swelling.