Selection of patients
We conducted a single-centre prospective study. One hundred and twelve consecutive patients who presented with acute arthritis of suspected microcrystalline origin were included in the study between October 2012 and May 2014. Clinical suspicion of crystal-induced arthritis was based on the following criteria: an acute onset (<10 days duration), swelling of one or few joints (up to three), local and or systemic signs and symptoms of inflammation, and absence of a known diagnosis of inflammatory rheumatic disease such as rheumatoid arthritis, spondyloarthritis or connective tissue disease. Our local ethical committee (Commission d’éthique de la recherche sur l’être humain (CER-VD)) approved the study. Consent to participate to the study was obtained from all patients.
Clinical data
For each patient, we collected demographic data, history of comorbidities known to be associated with gout (metabolic syndrome, renal impairment, medications that induce hyperuricemia, cardiovascular disease) and CPP (renal insufficiency, calcium/phosphate abnormalities, hypothyroidism). We also recorded previous history of arthritis flares. Because the duration of the illness reflected by previous crisis was suspected to be an important factor influencing the development of US signs, we performed a subset analysis, stratifying the patients into two groups: the former with previous crisis of CCP or MSU arthritis, the latter with none. We also recorded a detailed description of the current clinical presentation: number and localisation of symptomatic joints, duration of symptoms, local and systemic clinical signs such as joint temperature and/or redness presence of extra-articular tophi, C-reactive protein (CRP), uric acid blood levels, ongoing treatments for the current flare, and change in treatment induced by analysis of the synovial fluid.
Ultrasound
All patients underwent US of the symptomatic joint as well as both knees, ankles and the first metatarsophalangeal (MTP) joints. Each joint was explored using both longitudinal dorsal and lateral approaches. In the knee, a transversal supra-patellar view in maximal flexion was also performed to better examine the condylar cartilage. The machines used were either a Philips HD11 or an Esaote My-lab 70 philips: Best, Netherland Easote. Genoa, Italy. The type of probe was adapted to the size of the joint (from 9 to 18 MHz).
US diagnosis was evaluated based on typical US signs [11, 24]. For gout, we took into account the ‘double contour sign’ (Fig. 1a) and/or the presence of tophi, defined as a non-homogeneous mass that could be hypoechoic or hyperechoic, surrounded by a small anechoic rim (Fig. 1b). Hyperechogenic spots considered as aggregates of crystals were not considered. For CPP, intra-cartilage (Fig. 1c), meniscus (Fig. 1d), synovial or tendon hyperechoic deposits were considered diagnostic. Other US signs not necessarily relevant for the diagnosis were also recorded. They included erosions, osteophytes and Doppler activity in the synovium or around tophi. Symptomatic joints were examined first, followed by all other joints.
Two rheumatologists who were not aware of the clinical history or examination performed all US examinations. One rheumatologist has over 15 years of experience, and the other 2 years of experience. To determine the inter-observer agreement, the first 10 patients were examined in common by the two operators.
Joints aspiration and examination
Joint aspiration for microbiology and crystal analysis was performed on the symptomatic joints. Many of the aspirations were carried out under US guidance, especially when small joints were symptomatic or when little synovial fluid was present. US and joint aspiration were performed usually at the same time, but at most within 24 hours of each other.
Identification of crystals was based on crystal birefringence and crystal morphology. Only intracellular crystals were taken into account for diagnosis. The diagnosis was confirmed by two different observers (one directly after the puncture by the clinician; the other a technician in the laboratory dedicated to joint fluid analysis). In the laboratory, the fluid was first centrifuged in order to enhance the concentration of cells and of potential crystals. In the 10 cases where the amount of liquid was too small to be sent to the laboratory, the diagnosis was only based on clinician observation. In three cases of disagreement between the two observers, the laboratory diagnosis was retained.
A synovial fluid culture was also performed in each case to exclude septic arthritis. When the amount of fluid was adequate, a numeration of leukocytes was also performed to confirm the inflammatory nature of the acute flare.
X-ray imaging
X-ray imaging were recommended but not mandatory. Available X-ray imaging at the time of the acute attack were compared with US findings. Symptomatic and non-symptomatic joints were analysed separately. X-ray imaging were reviewed in consensus by two different rheumatologists as well as a musculoskeletal radiologist, all blinded to the final diagnosis. Radiological signs of gout were well-defined juxta-articular sclerotic erosions ± localised soft tissue swelling compatible with tophi, and CPP signs were linear radiopaque deposits projecting on articular soft tissues, in particular the cartilage, meniscus, tendons or synovium.
Statistical analysis
Results for quantitative clinical and demographic variables are reported as the mean ± standard deviation, and results for qualitative variables as numbers or percentages per category. The groups were compared by univariate logistic regression. P <0.05 was considered significant.
US and X-ray diagnoses were considered as index tests, with crystal identification in the fluid analysis considered the referent test for the diagnosis. The performance of US and X-ray imaging was evaluated by assessing the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) on symptomatic joints and also in all joints. Tests were performed using statistical software (MedCalc Software, Ostend, Belgium).