Distinguishing Gouty Arthritis from Calcium Pyrophosphate Disease and Other Arthritides

DISCUSSION

In our retrospective study of 225 acutely affected joints we evaluated the utility of the DC sign, joint hypervascularization in Doppler power color mode, and SUA levels and their combinations in diagnosing CRA (as well as their capability to differentiate gout from CPPD and other arthropathies). The gold standard of diagnosis was SF analysis according to the European League Against Rheumatism recommendations¹⁷.

In the literature the DC sign is attributed to a high specificity for gout^8,9,10,11,12. However, various studies have no or very low numbers of cases with CPPD in their control groups^{9,10,11,12,18}, or they limit their investigations to metatarsophalangeal and/or knee joints^9,10,19. If hyperechoic depositions in CPPD are densely accumulated, they can appear as continuous lines running parallel to the articular surface, making it very challenging if not impossible to distinguish them from the classic DC (Figure 1 A–D). Other authors have come to similar conclusions^14,15. It is our clinical experience that in acute arthritis with joint effusion, the definite allocation of sonographic hyperechoic cartilage enhancements to either the superficial margin as in gout or to the intracartilage area as in CPPD is rarely possible, even for experienced joint sonographers (Figure 1 E–F). In our investigation the DC sign was highly associated with CRA with good sensitivity and specificity and a high positive LR, but it could not differentiate the 2 crystal-related diseases. In the 5 cases in which hyperechoic enhancements were undoubtedly of intracartilage localization, the diagnosis CPPD was made in 100% of the cases. Notably, in 21 of 116 cases (18.1%) with positive DC sign, we found a non-CRA. Given its pathophysiology, a DC in the absence of crystalline disease seems like a paradox. One explanation could be the anatomy and shape of certain bones, which in some patients might lead to the false detection of a DC sign. Further, a DC is present not only during acute flares of CRA but also beyond that point^20,21,22. Some of our patients might have presented with an acute flare of a non-CRA while having asymptomatic hyperuricemia or even a history of CRA that was not present at the time of investigation but might have led to the formation of crystalline joint deposits in the past.

We have limited our investigation to the acutely affected joint at disease flare. Others have extended their US studies to more joints; however, they included patients not presenting with an acute clinical exacerbation of arthritis and with an exclusive history of gout^20,21. These authors detected US findings in clinically unaffected joints attributable to gout. Perhaps in acute arthritis it is possible to improve the diagnostic value of the US if clinically healthy joints are included into the examination, as Lamers-Karnebeek and colleagues have recently suggested²².

Very few studies included Doppler signals in their evaluation^19,21. Doppler/Duplex is often used to successfully detect even subclinical synovitis, but most studies have dealt with non–crystal-related joint diseases^23,24,25. In our study, higher degrees of hypervascularization (≥ degree 2) in power color mode were associated with gout and made that diagnosis more likely than CPPD or non-CRA (Figure 4). In combination with the DC sign, specificity for gout increased. This could be explained by the high inflammatory potential inherent to CRA, involving not only the immune system’s cellular components but also the joint’s vasculature³. Whether CPPD has a lesser inflammatory momentum than gout is purely speculative and clinically doubtful. Further studies including Doppler/Duplex examinations in the field of CRA are warranted.

It is well accepted that gouty arthritis occurs more frequently in hyperuricemic patients^4,17; however, it is likewise accepted that SUA levels can be normal in acute gouty arthritis while individuals with elevated UA might never be symptomatic¹⁷. Although mean UA levels in patients with gout were significantly higher than in any other disease group in our study (Figure 5), one can neither establish the diagnosis of gout nor rule out any other joint disease when relying solely on SUA. However, our data suggest that the concomitance of DC, hypervascularization, and elevated UA makes a diagnosis of gout 7 times more likely than one of CPPD or non-CRA. Moreover, in this case the PPV for gout is almost 89% and the specificity for gout rises to 92%. We propose a diagnostic algorithm (Figure 6) that can guide the clinician. The low sensitivity of 42% for gout, however, must be kept in mind, and means that a DC sign in the absence of either elevated UA or hypervascularization or both makes gout and CPPD equally likely (55.2% vs 44.8%). Hence, SF analysis is still required to confirm the diagnosis.

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Figure 6.

Possible diagnostic algorithm to differentiate gout, CPPD, and non-CRA. Of the 225 total cases, the missing ones are the 9 cases with coincidence of gout + CPPD. Below each branch, the absolute numbers in relation to total assurance of the diagnosis are given. Non-inflamm.: noninflammatory joint disease; CPPD: calcium pyrophosphate deposition disease; non-CRA: non–crystal-related inflammatory arthropathies; DC: double contour; UA: uric acid.

Interestingly, we detected 9 cases of simultaneous gout and CPPD. To our knowledge there are no reports of the kind published so far. The great majority of these cases had a positive DC sign and was strongly vascularized. A profound statistical statement, however, cannot be made.

Our work has some limitations that should be addressed. This study is retrospective in design. The cases were recruited from our clinical routine and therefore a total of 6 physicians performed the US. All sonographers were trained in joint sonography by DEGUM standards. However, the level of experience varied. In difficult or uncertain cases, a less experienced examiner consulted more experienced colleagues to verify findings. This procedure, however, was not standardized and could affect the sonographic results. The US findings were not routinely confirmed by a second sonographer blinded to the first results. Our US examinations focused on cartilage enhancements and Doppler flow. Other signs such as erosions, tophi, or tendon pathologies were not taken into consideration^11,26. The types of joints in our study were predominantly knees and ankles because these are common sites for CRA and other inflammatory joint diseases. For a separate evaluation for each joint, the study cohort lacked the appropriate case numbers.

Our data suggest that in daily clinical routine outside highly specialized joint sonography centers (like those of Filippucci^12,19, Grassi^8,26, and colleagues, for instance) the sonographic DC sign is highly specific for CRA but not for gout in particular. However, this specificity can be decisively increased by easy and commonly available instruments such as the Doppler-based evaluation of hypervascularization and determination of SUA levels. Further studies are required to facilitate and ensure the diagnosis in patients with acute monoarthritis and oligoarthritis with noninvasive techniques, especially for patients in whom joint puncture is contraindicated.