Definite Differences in Diagnosis? My Best News From ACR2014

November 21, 2014

(ACR2014) Our rheumatologist correspondent found three issues of particular interest: a biomarker test that has gone quickly to market, new diagnostic criteria for gout, and the potential of ultrasound for Sjögren syndrome.

Besides the update of 2012 guidelines for rheumatoid arthritis, which I wrote about previously, three issues relating to diagnosis stood out to me this year at the American College of Rheumatology annual meeting in Boston: More news about a biomarker test that has gone quickly to market, new diagnostic criteria for gout, and the potential ultrasound for diagnostic scoring of Sjögren syndrome.

The 14-3-3 Biomarker Test(s). I did continue my search to understand serum 14-3-3n and its role in rheumatoid arthritis this week.  I found that serum 14-3-3 is a protein with 7 isoforms. Only one isoform, 14-3-3n, is suggested to be associated with inflammatory arthritis. Other isoforms may be expressed in other diseases, such as aortitis.  

The 14-3-3n protein is reported to be synthesized in synovial tissue and expressed in the serum during joint space inflammation.  

I had the pleasure of meeting with Lance Feller MD from the St Louis University School of Medicine at poster 400.  Dr Feller and his colleagues were as surprised as I with the rapid progression of 14-3-3n to a commercial test for rheumatoid arthritis.  

His preliminary data in an early inflammatory arthritis cohort suggested that 32 of 132 patients demonstrated 14-3-3, but 16 patients had rheumatoid arthritis, 4 patients had JIA, and the remaining 12 had other diagnoses, including SLE and scleroderma.  

In another poster presentation, this one from Gilles Boire of the University of Sherbrooke in Quebec, entitled "88% of recent onset polyarthritis patients are positive for 14-4-3n markers and 14-3-3n auto-antibodies inform a favorable prognosis," 50% of patients were positive for 14-3-3n, but 85% were positive for the antibody to this protein.  Together, they represented some expression of protein or some antibody in 88% of patients studied.  

However, 38% were positive only for the antibody, and they had less joint progression. Dr Boire and colleagues suggested that the antibody clearance portends a positive prognosis, suggesting that the 14-3-3 protein may cause joint destruction.  

Dr. Dirkjan van Schaardenburg presented his data on the correlation of expression of this protein in active RA and the decrease in serum level with improvement in DAS28/EULAR response.  He defined RA outside of this protein expression  Perhaps it is noteworthy that 14-3-3n testing was performed by different laboratories for these presentations; Dr Schaardenburg and Dr Boire used Augurex Life Science Corps from Vancouver, British Columbia while Dr Feller used Quest Diagnostics, with headquarters in Madison NJ.  I am afraid we will have to wait to hear Dr Maksymowych's data for another time.

There seems to be a reproducible association of this group of proteins, and this isoform, with inflammatory disorders. However, the diagnostic specificity remains uncertain to me.  This may be a reflection of the techniques in different laboratories or different sites. Coupled with earlier data on infectious arthritis, this would suggest we have more to learn about serum 14-3-3n and its antibodies.

New Diagnostic Criteria for Gouty Arthritis. This was an exciting innovation, since it did yield evidence and utility for advanced imaging in the diagnosis of gouty arthritis.  Diagnostic criteria have always been meant to assist in enrollment in clinical trials, and this is no different; however, it also shows great promise to assist in clinical management.  

The researchers compared the proposed diagnostic criteria to the ARA criteria, Rome criteria, New York criteria, Mexico criteria, and Netherlands criteria. The New Diagnostic Criteria had a specificity of 0.92 and specificity of 0.89, the highest specificity and sensitivity of the criteria available.  

A point system is applied for each of the domains listed by letters A through G, which correlates strangely with "one if by land, two if by sea..."  The scoring system is tabulated below.  A score of > 8 strongly correlates with a diagnosis of gout.  

As anticipated, it marks the second set of diagnostic criteria which use ultrasound as a feature.

CriteriaCategoriesScore
A. Pattern of involvementankle/midst1
 MTP12
B. Characteristics of episode(s) everONE1
 TWO2
 THREE3
C. Time-course of episodes(s) everOne typical1
 Recurrent2
D.  Clinical tophiPresent4
E.  Serum urate6 to <8 mg/dL2
 8 to <10 mg/dL

3

 = or >10 mg/dL4
F. Ultrasound or DECT PositivePresent4
G. X-ray gouty erosionPresent4

Ultrasound and Sjögren's Syndrome:  Finally, during the session "Sjögren's Syndrome I:  Clinical Perspectives"  Chiara Baldini MD presented "Longitudinal Examination with Salivary Gland Ultrasonography of Patients with Primary Sjögren's Syndrome:  A Single Center Experience," which favorably compares the sonographic scoring system of the parotid and submandibular salivary glands with the conventional scoring system, the ESSDAI (European Sjögren's Syndrome Disease Activity Index).  

There were a subset of patients whose ultrasound characteristics were discordant with the ESSDAI, raising some question whether salivary gland ultrasound has either additional information or divergent information from the ESSDAI.  Further study is needed, but great promise was shown in this paper.  

In my first article, I mused whether the 2014 Boston ACR would bring the revolution its city's roots would promise. Perhaps some seeds of change have been sown. We can only know when we see what happens at San Francisco in 2015.