Gout is caused by the formation and deposition of monosodium urate crystals (MSU) in joints, or by forming usually extra-articular nodules called tophi. For the crystals to form, uric acid concentrations above 6.8mg/dL in blood are required, which is the saturation point for1,2 MSU .Once formed, the crystals remain in the joint cavity indefinitely while hyperuricemia, persists and over time the deposit increases and affecting more joints. However, the deposition of crystals may be reversed and, if the concentration of uric acid decreases, the crystals are dissolved and gout can be considered cured.3,4

As recommended by the EULAR working group for the treatment of gout, hypouricemic treatment goal is to promote the dissolution of the crystals and prevent their formation; this is achieved by maintaining a serum uric acid concentration below the saturation point for MSU: ≤6mg/dL (360≤mol/L).5,6

Various trials and cohort studies have shown an inverse correlation between serum uric acid levels during treatment and the speed with which the subcutaneous tophi7,8 are reduced. The reduction of uric acid below 6mg/dL is associated with not only a progressive reduction of subcutaneous tophi, but also reducing the size of the deep tophi, not accessible to physical examination and yet others detectable by imaging techniques such as ultrasound and magnetic resonance imaging (MRI).8 Since these techniques are valid for determining the size of tophi and their location, it is of great interest to know their usefulness in evaluating the effectiveness of hypouricemic treatment, which helps decide not only when to use hipouricemic agents in patients with gout but also when to intensify treatment or whether it could be reduced or even suspended.

Therefore, the objective of this systematic review is to analyze the published evidence on the usefulness of ultrasound and MRI in the evaluation of treatment response in patients with gout.

We selected studies that evaluated the response to treatment of patients with gout (NSAIDs hipouricemic agents, etc., regardless of type, dose and duration of treatment) using imaging (ultrasound and/or MRI) in patients with gouty arthritis (selected regardless of the criteria for diagnosis, type and number of joints affected). We selected articles that measured correlation coefficients, sensitivity to change, changes after treatment using radiological and clinical variables (number of attacks, number of swollen joints, uric acid levels, number of tophi, disappearance of tophi, quality of life and laboratory data), variables related to safety, etc. Regarding the design of the studies, meta-analyses, systematic reviews, clinical trials, cohort and validation studies were included. Basic science articles and animal studies were excluded.

We searched the following electronic databases until February 2012: MEDLINE (from 1960), EMBASE (from 1980) and the Cochrane Library (Central). We searched both MeSH terms and free text formats. No limits were set on the publication date. In addition, we searched abstracts sent to ACR and EULAR meetings in 2010 and 2011. Finally, a manual search for articles finally included was performed. The specific search strategy is detailed in the supplementary material (see Appendix annex).

A single reviewer (VV) analyzed the articles resulting from the search as well as the detailed analysis of the items included. The first search result was filtered by title and abstract or entire article in case they were not summarized by 20min maximum duration sessions. If in doubt, a second reviewer (EL) resolved the discrepancy. After this process, the remaining items were analyzed in detail (VV). Again, if in doubt, EL would solve it. Finally, a manual search with references selected for detailed analysis was performed. All Internet references were retrieved and placed in the EndNote software to facilitate management.

To assess the methodological quality of included studies we used: (a) for clinical trials, the Jadad scale (1–5; considering good quality studies as Jadad 3–5), and (b) for cohort studies, the Oxford quality scale.

The search results are detailed in Fig. 1.

Fig. 1.

Flowchart of included articles.

(0.09MB).

In this systematic review of the literature we analyzed the value of ultrasound and MRI in the evaluation of treatment response in patients with gouty arthritis. To achieve this goal, we conducted an extensive search on the main bibliographic databases available, as described in the Materials and Methods section. After detailed analysis of the selected studies, only three studies were included that examined the utility of ultrasound to evaluate the response to treatment, 2 published in international journals and one9,10 presented solely as a poster at EULAR.11 All were case series conducted at a single center with a small number of patients (level of evidence 3a on the Oxford quality scale). There were no studies evaluating the response to treatment with hypouricemic drugs using MRI. It represents one of the main limitations of this review, which should be kept in mind when evaluating the findings.

Regarding patients studied,9–11 all had gouty arthritis diagnosed by detecting MSU crystals in the synovial fluid with a polarized light microscope, all had baseline uricemia values above EULAR recommendations (>6mg/dL) and in the 2 studies analyzed10,11 all patients had a baseline ultrasound “double contour” sign (deposits of uric acid crystals in hyaline cartilage, which increases the cartilage surface interface thickness reaching something similar to the subchondral bone). Determinations of uric acid at baseline and at each follow-up visit were performed, and hypouricemic treatment was adjusted based on the EULAR recommendations.5,6

Although the included studies were heterogeneous in terms of the clinical and sonographic variables collected, all of them showed the reduction of serum uric acid to be significantly correlated with improved ultrasound findings: decline and even disappearance of the “double contour” sign in patients with uric acid below 6mg/dL in the studies by Thiele and Schlesinger10 and Peiteado et al.,11 and reduction of the maximum transverse diameter and volume of tophi in the study by Perez-Ruiz et al.9

Ultrasound has been shown to be an imaging technique sensitive to change for inflammatory activity present in patients with different inflammatory rheumatic diseases, including gout, allowing us to objectify synovitis or tendinitis and quantify the Doppler signal intensity. It has also proven to be more sensitive than plain X-rays in the early detection of bone erosions, displaying the structural damage to tendons and entheses and being capable of detecting tophi < cm 1, which are difficult to detect even by MRI.12–16

Although based on what has been commented previously it seems logical that ultrasound could be a useful technique in the evaluation of response to treatment with hypouricemic agents in patients with gout, there is little information published in the literature to analyze this aspect. With the studies currently available, we can only say that ultrasound may be useful for evaluating the response to hypouricemic treatment in patients with gout with a 3a level of evidence and a B degree of recommendation. However, taking into account the limitations encountered in this systematic review, we believe that larger studies (randomized clinical trials, cohorts, etc.) will be needed to confirm these results.

As for MRI, although published studies in the literature have shown its reliability in the detection and measurement of tophi, there is currently no evidence to evaluate its usefulness in the treatment response of patients with gout.

The authors declare no conflicts of interest.