Ultrasound imaging in crystal arthropathies: a pictorial review.

OBJECTIVE: The prevalence of crystal arthropathies in the general population is rising. The purpose of this pictorial study is to describe the sonographic elements of the most prevalent crystal arthropathies by emphasizing particular sonographic findings using illustrative images and cases while considering technical details and common pitfalls. METHODS: Using established recommendations, specialists in the fields of sonography and crystal arthropathies agreed by consensus on the unique ultrasound signs associated with each of the conditions. RESULTS: Gout, calcium pyrophosphate deposition arthropathy, and hydroxyapatite arthropathy are the three most prevalent crystal arthropathies. Today's high-resolution sonography enables reliable evaluation of the underlying crystal deposits, post-inflammatory changes, and a precise description of joint inflammation. CONCLUSIONS: High-prevalence crystal arthropathies are reliably detectable by ultrasound with current ultrasound equipment. It is necessary to have extensive ultrasound training, know specific sonographic findings, and understand all possible differential diagnoses for disorders affecting the musculoskeletal system.

ACR Appropriateness Criteria® Chronic Extremity Joint Pain-Suspected Inflammatory Arthritis, Crystalline Arthritis, or Erosive Osteoarthritis: 2022 Update.

Evaluation for suspected inflammatory arthritis as a cause for chronic extremity joint pain often relies on imaging. It is essential that imaging results are interpreted in the context of clinical and serologic results to add specificity because there is significant overlap of imaging findings among the various types of arthritis. This document provides recommendations for imaging evaluation of specific types of inflammatory arthritis, including rheumatoid arthritis, seronegative spondyloarthropathy, gout, calcium pyrophosphate dihydrate disease (or pseudogout), and erosive osteoarthritis. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Crystal arthropathies and osteoarthritis-where is the link?

Osteoarthritis (OA) is one of the leading causes of disability worldwide. As our understanding of OA progressively has moved from a purely mechanical "wear and tear" concept toward a complex multi-tissue condition in which inflammation plays a central role, the possible role of crystal-induced inflammation in OA incidence and progression may be relevant. In addition to gout, which affects 4% of the US population, basic calcium phosphate and calcium pyrophosphate deposition both may induce joint inflammation and may play a role in pain in OA. This narrative review article discusses the possible mechanisms underlying the associations between crystal-induced arthropathies and OA, and the important implications of these for clinical practice and future research.

Imaging of Crystal Disorders:: Calcium Pyrophosphate Dihydrate Crystal Deposition Disease, Calcium Hydroxyapatite Crystal Deposition Disease and Gout Pathophysiology, Imaging, and Diagnosis.

Crystal arthropathies are a group of joint disorders due to deposition of crystals in and around joints that lead to joint destruction and soft tissue masses. Clinical presentation is variable and diagnosis might be challenging. In this article the pathophysiology is addressed, the preferred deposition of crystal arthropathies and imaging findings. Case studies of calcium pyrophosphate dihydrate crystal deposition disease, hydroxyapatite crystal deposition disease, and gout are shown. Guidelines for the use of dual-energy computed tomography are given to enable the diagnosis and follow-up of gout.

Acute haematogenous periprosthetic joint infection due to Streptococcus sanguinis along with coexistent crystalline arthropathy after total knee arthroplasty: a rare combination.

A man in his 60s, with a medical history of gout, underwent total knee arthroplasty of his right knee followed by expeditious rehabilitation. Seven months after surgery, he was referred to the emergency ward with sudden onset of pain and swelling of his right knee accompanied with fever. Further inquiry revealed no trauma, infection or skin lesions besides a tongue bite several weeks earlier. An impaired range motion of the knee was seen on physical examination along with a tachycardia. Laboratory studies showed a C reactive protein of 345 mg/L, after which a debridement, antibiotics and implant retention procedure was performed. Intraoperatively obtained synovial fluid showed monosodium urate crystals consistent with crystalline arthropathy (ie, gout). However, unexpectedly, Streptococcus sanguinis was identified in all microbiological cultures too, confirming a coexistent periprosthetic joint infection. After comprehensive antibiotic treatment and gout flare therapy, this patient made a full recovery with retention of the implant.

Factors Affecting Response to Anakinra in Crystalline Arthritis Flares.

BACKGROUND: Interleukin 1 inhibition with anakinra has shown efficacy in the management of crystalline-induced arthritis (CIA) flares. Gout treatment guidelines recommend its use after contraindication or intolerance to first-line therapies. The aim of this study is to identify features associated with better response to anakinra when used to treat CIA flares. METHODS: This is a medical record review study that included inpatients with acute CIA in whom anakinra was used between the years 2014 and 2019 at one tertiary center (University of Alabama at Birmingham). The primary end point was response to anakinra treatment defined as a decrease in the reported visual analog score of at least 50% within 48 hours of initiation of treatment. Demographic, clinical, and laboratory factors were compared, and factors found significant in bivariate analysis at a p value of less than 0.15 were tested in a multivariate logistic regression analysis for independent association with the response. RESULTS: A total of 55 admission encounters were analyzed. The mean age was 60.1 years, 36 (66%) were men, and 31 (56%) were African Americans. Twenty-eight of 49 (57%) met the primary end point of response at 48 hours, but 52 of 55 (94.5%) ultimately responded to anakinra during hospital stay. Factors associated with response at 48 hours were race, reason for admission related to cardiac etiologies, not having failed steroids before trial of anakinra, and hospital admission within 48 hours of initiation of flare. On a multivariable logistic regression model, we could not find significant independent associations with response to anakinra. CONCLUSIONS: Our study showed high response rates to anakinra. We could not identify factors associated with a more robust, early response. It is likely that anakinra is equally effective across a wide range of clinical scenarios.

Acute Calcium Pyrophosphate Crystal Arthritis of the Wrist Elicited by Anti-COVID-19 Vaccination After Carpal Tunnel Release.

BACKGROUND Calcium pyrophosphate dihydrate deposition disease includes a variety of clinical syndromes, including acute calcium pyrophosphate (CPP) crystal arthritis. Most patients with CPP crystal arthritis have a primary/idiopathic form presenting with severe pain, swelling, and stiffness. COVID-19 infection, which originated in China in December 2019, required extraordinary efforts to develop and test new vaccines to halt the pandemic. The Vaxzervria vaccine has shown excellent safety and efficacy in phase 3 trials with a mechanism based on the expression of the SARS-CoV-2 spike protein gene coding for the S-antigen, which stimulates the immune response. CASE REPORT We describe an acute event of crystal arthritis after a carpal tunnel syndrome release followed by administration of the second dose of anti-COVID-19 Vaccine Oxford-AstraZeneca (ChAdOx1 nCoV-19). Medical treatment resulted in full resolution of the symptoms in 2 weeks. CONCLUSIONS Although most episodes of acute arthritis happen spontaneously, certain factors may trigger the acute CPP crystal arthritis such as intercurrent illnesses or surgeries. Although the association between carpal tunnel syndrome and CPP arthritis has been known for over 40 years, surgical release of the carpal ligament has always been associated with full resolution of symptoms. This is the first case report describing an exacerbation after carpal canal release, concomitant with the administration of the vaccine. According to our opinion, the vaccination associated with a prior surgery in the same anatomical site could have synergically triggered the arthritis flare-up, in a predisposed patient, with a mechanism still unknown.

Distinguishing Periprosthetic Crystalline Arthropathy from Infection in Total Knee Arthroplasty: A Systematic Review.

Distinguishing periprosthetic crystalline arthropathy from periprosthetic joint infection (PJI) remains a diagnostic challenge as both symptom presentation and diagnostic tests overlap. Accurate differentiation is important as treatment plans vary significantly. We sought to systematically review all cases of total knee arthroplasty (TKA) periprosthetic crystalline arthropathy reported in the literature and summarize clinical, diagnostic, and operative findings in the context of guidelines for diagnosing PJI. The goal of this systematic review is to determine the amount of diagnostic overlap and to identify best practices for differentiating between these two diagnoses. MEDLINE and Google Scholar were searched to identify cases of crystalline arthropathy following TKA. Case reports were reviewed for patient characteristics, clinical symptoms, physical exam, laboratory results, and treatment outcomes. These findings were summarized across patients and dichotomized based on current thresholds for diagnosing PJI according to Musculoskeletal Infection Society criteria. Twenty-six articles were identified which included 42 cases of periprosthetic crystalline arthropathy (17 gout, 16 pseudogout, one both, and eight not specified). Of these cases, 25 presented over 1 year after their index arthroplasty and 15 had no prior history of crystalline arthropathy. Only six cases had a superimposed infection based on aspiration or intraoperative cultures. For cases without a culture-positive infection, several diagnostic tests overlap with PJI thresholds: 95% of patients had C-reactive protein greater than 1 mg/dL, 76% had an erythrocyte sedimentation rate greater than 30 mm/hour, 91% had a synovial white blood cell greater than 3,000 cells, and 76% had a synovial polymorphonuclear cells percent greater than 80%. Patients without co-infection were managed with non-steroidal anti-inflammatory drugs, colchicine, allopurinol, steroids, or a combination of these treatments and most had complete resolution of symptoms within 1 week. Commonly used markers of PJI fail to reliably distinguish periprosthetic crystalline arthropathy from infection. Though clinical judgement and consideration of the implications of delayed treatment for acute PJI remain paramount, in the setting of synovial crystals, surgeons may wish to consider this alternate etiology as the source of the patient's clinical symptoms.

Identifying Potential Classification Criteria for Calcium Pyrophosphate Deposition Disease: Item Generation and Item Reduction.

OBJECTIVE: Classification criteria for calcium pyrophosphate deposition (CPPD) disease will facilitate clinical research on this common crystalline arthritis. Our objective was to report on the first 2 phases of a 4-phase process for developing CPPD classification criteria. METHODS: CPPD classification criteria development is overseen by a 12-member steering committee. Item generation (phase I) included a scoping literature review of 5 literature databases and contributions from a 35-member combined expert committee and 2 patient research partners. Item reduction and refinement (phase II) involved a combined expert committee meeting, discussions among clinical, imaging, and laboratory advisory groups, and an item-rating exercise to assess the influence of individual items toward classification. The steering committee reviewed the modal rating score for each item (range -3 [strongly pushes away from CPPD] to +3 [strongly pushes toward CPPD]) to determine items to retain for future phases of criteria development. RESULTS: Item generation yielded 420 items (312 from the literature, 108 from experts/patients). The advisory groups eliminated items that they agreed were unlikely to distinguish between CPPD and other forms of arthritis, yielding 127 items for the item-rating exercise. Fifty-six items, most of which had a modal rating of +/- 2 or 3, were retained for future phases. As numerous imaging items were rated +3, the steering committee recommended focusing on imaging of the knee and wrist and 1 additional affected joint for calcification suggestive of CPP crystal deposition. CONCLUSION: A data- and expert-driven process is underway to develop CPPD classification criteria. Candidate items comprise clinical, imaging, and laboratory features.

Mechanosensitive TRPV4 is required for crystal-induced inflammation.

Crystal structures activate innate immune cells, especially macrophages and initiate inflammatory responses. We aimed to understand the role of the mechanosensitive TRPV4 channel in crystal-induced inflammation. Real-time RT-PCR, RNAscope in situ hybridisation, and Trpv4eGFP mice were used to examine TRPV4 expression and whole-cell patch-clamp recording and live-cell Ca2+ imaging were used to study TRPV4 function in mouse synovial macrophages and human peripheral blood mononuclear cells (PBMCs). Both genetic deletion and pharmacological inhibition approaches were used to investigate the role of TRPV4 in NLRP3 inflammasome activation induced by diverse crystals in vitro and in mouse models of crystal-induced pain and inflammation in vivo. TRPV4 was functionally expressed by synovial macrophages and human PBMCs and TRPV4 expression was upregulated by stimulation with monosodium urate (MSU) crystals and in human PBMCs from patients with acute gout flares. MSU crystal-induced gouty arthritis were significantly reduced by either genetic ablation or pharmacological inhibition of TRPV4 function. Mechanistically, TRPV4 mediated the activation of NLRP3 inflammasome by diverse crystalline materials but not non-crystalline NLRP3 inflammasome activators, driving the production of inflammatory cytokine interleukin-1ß which elicited TRPV4-dependent inflammatory responses in vivo. Moreover, chemical ablation of the TRPV1-expressing nociceptors significantly attenuated the MSU crystal-induced gouty arthritis. In conclusion, TRPV4 is a common mediator of inflammatory responses induced by diverse crystals through NLRP3 inflammasome activation in macrophages. TRPV4-expressing resident macrophages are critically involved in MSU crystal-induced gouty arthritis. A neuroimmune interaction between the TRPV1-expressing nociceptors and the TRPV4-expressing synovial macrophages contributes to the generation of acute gout flares.

Synovial fluid cell count of 84 930/mm3 in adult-onset Still's disease.

In traditional teaching, synovial fluid cell counts over 50 000/mm3 are in keeping with septic or crystalline arthritis. We report a patient with adult-onset Still's disease (AOSD) and associated inflammatory arthritis whose synovial fluid cell count was over 80 000/mm3 This is the highest level reported in the literature, demonstrating that in the appropriate clinical context, markedly elevated synovial cell count levels over 50 000/mm3 can be caused by inflammatory conditions like AOSD. Recognition of this is crucial to avoid inappropriate antibiotics and procedures while also ensuring correct immunosuppressive treatments are offered in a timely manner.

[Diagnostic approach and differential diagnosis of mon- and oligoarthritis]. / Wichtige Differenzialdiagnosen von Mon- und Oligoarthritiden.

Reasons of mon- and oligoarthritis are heterogeneous. The diagnostic approach includes a detailed medical anamnesis, physical examination and imaging (conventional X-ray, sonography, MRI and, CT). Analysis of the synovial fluid is required in suspected septic arthritis and frequently helps in diagnosis and differential diagnosis of crystal arthropathies. Dual-energy-CT (DECT) detects sodium urate crystals and can replace joint puncture in some cases. In addition to crystal arthropathies and septic arthritis, differential diagnosis of mon-/oligoarthritis includes reactive arthritis, arthrosis and monarthritic courses of SpA/PsA. A rheumatologist should be consulted particularly in the case of persistent monarthritides, in order to initiate a specific therapy to prevent secondary damage.

Synovial fluid presepsin as a novel biomarker for the rapid differential diagnosis of native joint septic arthritis from crystal arthritis.

OBJECTIVE: To investigate whether presepsin can be used as a novel biomarker to differentiate between native joint septic arthritis (NJSA) and crystal arthritis (CA). METHODS: This study included 75 patients diagnosed with either NJSA (n = 21) or CA (n = 54). Presepsin in synovial fluid and blood, C-reactive protein, and procalcitonin were measured and compared between the NJSA and CA groups. Receiver operating characteristic (ROC) curve analyses were performed to differentiate between the two groups. RESULTS: Synovial fluid and blood presepsin were significantly higher in the NJSA group than in the CA group (p < 0.0001 and p < 0.01, respectively). The area under the ROC curve for synovial fluid presepsin in the NJSA group compared with the CA group was 0.93 (sensitivity 85.7%, specificity 85.2%, positive predictive value 69.2%, negative predictive value 93.9%, positive likelihood ratio 5.79, negative likelihood ratio 0.17). Among the tests, synovial fluid presepsin was the most accurate. CONCLUSIONS: Measurement of synovial fluid presepsin is reliable for the early diagnosis of NJSA, and synovial fluid presepsin could be used as a novel biomarker for differentiating between NJSA and CA.

Clinical implications of synovial fluid specimen handling for crystal associated arthritides: A systematic review.

AIM: To identify the appropriate methods of synovial fluid (SF) specimen storage, manipulation and handling for crystal associated arthritides (CAA) diagnosis. METHOD: A systematic literature review was conducted using 5 medical databases to identify diagnostic studies assessing SF specimen handling for calcium pyrophosphate (CPP) and monosodium urate (MSU) crystals identification. All included studies were rated for quality using the Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS: Fifteen studies, including 2 non-English language manuscripts, were included. Eight studies examined both types of crystals, while 3 studies examined CPP and 4 studies examined MSU crystals only. Overall, MSU crystals were more stable over time compared to CPP crystals. MSU stability was generally independent of time, preservative and temperature. CPP crystals deteriorated with time and were more stable if refrigerated. Ethylenediaminetetraacetic acid (EDTA) was a suitable preservative. Re-examining an initially negative SF sample at 24 hours facilitated detection of additional cases. Very few studies had an overall low risk of bias and applicability. CONCLUSION: Monosodium urate crystals remain stable over time independent of storage time, temperature and preservative. CPP crystals are mostly stable for 24-48 hours but can deteriorate with time. Overall, SF crystal examination should ideally be done within 24-48 hours. They may be stored at room temperature without any preservative. Otherwise, refrigeration (4°C/39°F) and EDTA preservation is reasonable. Stored SF re-examination, at 24 hours, helps identify a small number of additional MSU and CPP cases. Centrifugation techniques allow better and easier crystal identification, particularly CPP. Most studies were of unclear or low quality.