Each year, roughly coinciding with annual rheumatologist meetings, we have seen reports of the amazing ability to see uric acid crystals in places previously hidden. This year is no exception.

Whilst the latest report shows that DECT is not the ultimate gout diagnostic tool for all situations, it does have a firm place in the rheumatologist’s toolkit.

I have reported on DECT For Gout Diagnosis earlier, and there are several more references, which you can find by entering DECT into the search box above. The latest report was presented at ACR Annual Scientific Meeting in November 2011, and the abstract follows.

Diagnosis of Gout Using Dual-Energy Computed Tomography: An Accuracy and Diagnostic Yield Study

Authors

Tim Bongartz (Mayo Clinic, Rochester, Minn)
Katrina N. Glazebrook (Mayo Clinic, Rochester, Minn)
Steven J. Kavros (Rochester, MN)
Clement J. Michet (Mayo Clinic, Rochester, Minn)
Stephen P. Merry (Mayo Clinic, Rochester)
Naveen S. Murthy (Mayo Clinic, Rochester, Minn)
Bharath Manu Akkara Veetil (Mayo Clinic, Rochester, Minn)
John M. Davis III (Mayo Clinic, Rochester, Minn)
Thomas G. Mason II (Mayo Clinic Rochester, Rochester, MN)
Kenneth J. Warrington (Mayo Clinic, Rochester, Minn)
Nisha J. Manek (Mayo Clinic, Rochester, Minn)
Tanaz A. Kermani (Mayo Clinic, Rochester, Minn)
Deana D. Hoganson (Mayo Clinic, Rochester, Minn)
A. Kirstin Bacani (Mayo Clinic, Rochester, Minn)
Hailong Wang (Mayo Clinic, Rochester, Minn)
Cynthia H. McCollough (Rochester, MN)
Mayo Clinic Rochester, Rochester, MN

Background/Purpose

Dual energy computed tomography scanning (DECT) is highly accurate in detecting and classifying renal uric acid stones. This technology has recently been modified to detect intra- or peri-articular monosodium urate (MSU) deposits. We aimed to formally assess the accuracy of this new imaging method to diagnose gout and explore whether it may have any substantial impact on clinical decision making beyond the established diagnostic approach using polarizing microscopy of synovial fluid.

Method

To assess the sensitivity and specificity of DECT for diagnosis of gout, we included patients into two prospective cohorts: A control cohort of subjects without any history of gout who underwent arthrocentesis for other types of joint disease, and a second cohort of subjects with active gout diagnosed with a combined reference method of polarizing and electron microscopy. Accrual was stratified according to joint location and duration of symptoms (?6 weeks/6 weeks) in order to capture a wide spectrum of disease. All study participants underwent dual source, dual energy (80 and 140 kVP) CT scanning of the aspirated joint. Images were classified by a musculoskeletal radiologist as positive or negative for MSU deposition. To explore the diagnostic yield of DECT scanning, we assembled a third cohort of subjects who had clinical suspicion for gout but from whom an appropriate synovial fluid specimen for analysis could either not be obtained, or polarized microscopy was negative for the presence of MSU crystals. These subjects then had DECT imaging of the affected joint area. If the imaging findings suggested the presence of MSU deposits, we performed an ultrasound (US) guided aspiration of these areas with subsequent polarizing microscopy.

Result

The sensitivity and specificity of DECT for diagnosing gout was 0.93 (95%CI 0.79-0.98) and 0.95 (95%CI 0.82-0.99), respectively. These estimates were based on 40 patients with confirmed gout according to the reference method and 40 control patients with other types of joint disease. All 3 false negative subjects were observed in the stratum of 10 patients with acute podagra and no prior episodes of joint pain. The 2 false positive patients had advanced knee osteoarthritis with a DECT signal indicating intracartilaginous uric acid deposition. The diagnostic yield cohort consisted of 30 subjects with a clinical suspicion for gout but a negative synovial fluid aspiration. DECT imaging showed evidence for uric acid deposition in 14 of these 30 patients (46.7%). US guided aspiration of areas with positive DECT findings confirmed presence of MSU crystals.

Conclusion

DECT imaging provides high sensitivity and specificity for detection of MSU crystal deposits in subjects with gout. Sensitivity appears to be lower in patients with acute symptoms and no prior history of gout. DECT is a high-yield test with significant impact on clinical decision making when gout is suspected based on clinical presentation but polarizing microscopy of synovial fluid fails to demonstrate MSU crystals.

When Is DECT Best For Gout Diagnosis?

This investigation confirms the earlier findings that DECT is excellent at showing the location of uric acid crystal deposits around joints. As in earlier studies, the technique often shows crystals in joints before they are subjected to an acute gout flare.

Significantly, the researchers wanted to push the limits of the technology, and included new gout patients:

“We wanted to really challenge the new method by including patients who were only a few days into their first flare of gout”

Tim Bongartz – Lead Investigator

In the real world, such patients would not be investigated in-depth for their first attack, and this highlights the best use of DECT fo gout diagnosis. Since we know that it can detect uric acid crystals in situations that do not show in joint fluid analysis, then the perfect procedure for gout suspects is:

1. Wait to see if acute gout attacks repeat
2. Perform joint fluid analysis
3. If joint fluid analysis is negative, but gout is strongly suspected, arrange a DECT scan

Again, in the real world, most of us are a long way from this, as DECT facilities are few and far between. However, this does not prevent treatment, and so if gout is suspected, despite a negative joint fluid analysis, it may be best to start uric acid lowering treatment to get uric acid in the blood down to 5mg/dL (0.30mmol/L).

Leave When Is DECT Best For Gout Diagnosis? to browse the Gout Symptoms section…

The trouble with uric acid crystals, is you know they are there, but you cannot see them.

It’s worrying to know there are millions of tiny particles floating round your body, that remain hidden.

Now, strictly speaking, they don’t always remain hidden, as large deposits form tophi, that can break through the skin. But for our own peace of mind, and to help our doctors diagnosis and treatment, it really is a good idea to see what is happening in our joints.

Traditionally, the only way to test for the presence of uric acid crystals is to analyze fluid from the joints. Recently, there is hope that DECT might eventually replace this invasive procedure, but the huge expense of suitable scanning equipment puts this beyond the reach of most gout patients.

Advances in other medical imaging techniques leads to frequent reviews in professional journals. The most recent[1] of these concludes:

The diagnosis of gout is usually based on clinical presentation and laboratory findings. Imaging plays a role in the assessment and grading of articular damage related to chronic, long-standing disease, which is characterized by granulomatous synovitis, tophi, and erosions. Multimodality imaging of chronic tophaceous gout may be useful in clinical practice for a variety of purposes, including assessment of disease-related anatomical changes and monitoring of articular and soft-tissue lesions over time, especially in response to urate-lowering therapy. Radiography remains the primary imaging technique. Ultrasonography may detect monosodium urate crystals on cartilage, is helpful to assess small joint effusion, to guide to joint aspiration, and to evaluate the volume of tophi. Computed tomography is considered to be more sensitive than plain radiography in the detection and evaluation of cortical bone erosions associated with tophi. MRI represents the only imaging modality which provides visualization of bone marrow oedema associated with erosions and may be useful to characterize and distinguish tophi from other soft tissue nodules.

Unfortunately the full report is in Italian, and impossible for me to understand. However, an earlier review[2] shows similar findings, and so we can see how different technologies play their part in allowing us to see uric acid crystals (or not).

X-ray

Uric acid crystals will not show on x-rays. However, they do show joint damage where gout has eaten into the bone. Unfortunately, this is too late to prevent that damage.

Ultrasound

The relatively low cost, and high availability, of ultrasound makes it the most reliable tool for measuring gout progression. It will detect deposits at quite an early stage, though it will not determine if these are uric acid crystals from gout or other deposits such as pseudogout. If there is doubt, the ultrasound can also help in positioning the rheumatologist’s needle for joint fluid analysis.

CT Scans

Computed Tomography will detect uric acid crystals at very low volumes. It also shows clearly when these deposits start growing into bone – a much earlier recognition of bone damage compared to x-ray. Though this early detection of deposits allows urate lowering treatment to start before gout causes permanent damage, the scarcity of suitable equipment limits this to the lucky few.

MRI

MRI, though not cheap, is more widely available. It will detect bone erosion earlier then x-ray, and it will detect deposits, though not what they are. The 2009 study concludes that MRI might be most useful in assessing joint problems associated with gout, whilst the later report notes that it is the only technique to show bone marrow swelling [edema].

Leave this page to browse the uric acid crystals in the Understanding Uric Acid Section

References

1. Title:

   [Multimodality imaging of chronic tophaceous gout].

   Authors:

   Paparo F, Sconfienza LM, Muda A, Denegri A, Piccazzo R, Aleo E, Cimmino MA.

   Published:

   Reumatismo. 2010 Oct-Dec;62(4):286-91.

2. Title:

   Imaging of gout: findings and utility.

   Authors:

   Perez-Ruiz F, Dalbeth N, Urresola A, de Miguel E, Schlesinger N.

   Published:

   Arthritis Res Ther. 2009;11(3):232. Epub 2009 Jun 17. Uric Acid Crystals: X-ray, Ultrasound, MRI, & CT

…

The uric acid blood test is what warns us gouties that we are at risk of another acute gout attack.

This is very reliable for confirmed gout patients, but a source of extreme confusion and frustration for unconfirmed patients with gout symptoms.

Uric Acid Diagnosis Vs Uric Acid Management

There is a significant difference in interpreting uric acid blood test results between confirmed and suspected gout cases. For a confirmed gout patient, any number above 7mg/dL (0.4 mmol/L) is a clear risk of a gout attack. Blood tests for confirmed gouties should be used as an aid to managing gout. They indicate whether urate lowering therapy is set at the right dosage. This is a fairly simple process, though it does rely on the doctor understanding the need to set the right target uric acid level, and it relies on the patient taking the medication daily as directed.

The problems arise when a gout diagnosis is doubtful, and uric acid blood test results are being used to help form a definite diagnosis. There are two fundamental problems with this approach, which I explain below. Gout diagnosis from blood tests is possible, but needs a clear understanding of the gout process, preferably bolstered by more tests on a weekly basis.

We know that uric acid crystals can form in joints at normal temperatures with a uric acid concentration of slightly under 7mg/dL ^[1]. For confirmed gout patients, it is almost certain that uric acid will form crystals at that level. For unconfirmed gout patients, there is a strong probability that it will cause a gout attack, but this is not certain.

Uric Acid Blood Test Reporting Problem

After drawing a blood sample, your doctor sends this for analysis at a laboratory. Each lab has different procedures, but invariably they will report the actual test number plus an assessment of high, low, or normal.

Normal is dangerous.

It is not a medical assessment, just a statistical expression of how your results compare to hundreds of other people. This is often referred to as a reference range, and medically it is fairly meaningless. Who knows the sample to whom you are being compared? Are they undiagnosed gout or hyperuricemia sufferers? Nobody really knows or cares. The lab have simply used some textbook ranges, or done their own sampling and taken a percentage as “normal.”

This is pointless and very misleading. We already know that, medically, anything above 6mg/dL is not normal. 6 to 7 is risky, and above 7 is dangerous. Comparing the numbers to an average sample is meaningless.

I searched for “uric acid reference range calculation,” which yields the “normal” range for several laboratories. The ranges of my random sample are:

The very fact that they report different ranges for males and females should set alarm bells ringing. Yes, pre-menopausal females do have a lower likelihood of gout, but this is because physiologically they are likely to have lower uric acid levels – at the same uric acid level, they have the same gout risk.

From my small random sample, you could have uric acid as high as 8.5 mg/dL (0.51 mmol/L) and still be considered normal. Further interpretation often occurs with “slightly high” applied when just over the “normal” range. You really must get the exact number, but even that is not the full story.

Uric Acid Blood Test Temporary Decrease

We measure uric acid in the blood as a way of assessing the risk of uric acid crystals forming. After all, it is the presence of those crystals that causes the gout reaction, not uric acid in the blood. Generally speaking, blood uric acid concentration is a good indicator of uric acid concentration in the joints and tissues, but there is a problem when a gout attack starts.

Gout attacks occur in untreated gout patients when uric acid forms crystals in and around one or more joints. As soon as this happens, uric acid has left the bloodstream to concentrate in the gout attack site. This means that blood uric acid reported in a test at the beginning of a gout attack can be lower than normal. This does not happen every time, but often enough to prevent a definite diagnosis if uric acid levels have temporarily reduced due to the gout attack. The study that first reported this phenomenon ^[2] has been repeated by two other research groups. The studies clarify that uric acid concentration can rise or fall during a gout attack. Though the groups differ on percentages of patients showing a temporary fall in blood uric acid, they all agree that a single blood test at the time of an acute gout flare renders the test unreliable as a diagnostic.

Uric Acid Blood Test: Next Steps

Now that you understand the importance of real numbers, and not a range assessment, you should always insist that your doctor gives you the exact uric acid teat result, together with the range. This is a number followed by mg/dL or mmol/L, though occasionally other variations on these scales are used.

If you are told that your symptoms cannot be gout because your uric acid blood test result is normal, just say “No Thanks! I want a proper diagnosis”

Uric Acid Blood Test References

1. GoutPal. [Internet] [Cited 29th March 2010] Uric Acid Concentration
2. Logan JA, Morrison E, McGill PE. Ann Rheum Dis. 1997 Nov;56(11):696-7. Serum uric acid in acute gout. Serum Uric Acid In Acute Gout
…