How Often Is Primary Sjögren Syndrome Misdiagnosed?

Serological abnormalities such as rheumatoid factor (RF) and/or antinuclear antibodies (ANA) were associated with a subset of patients diagnosed with primary Sjögren syndrome (SS) after an initial, possibly mistaken, diagnosis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and/or systemic sclerosis (SSc), according to a study published in Rheumatology.  

Although primary SS is typically suspected in patients who have a history of dry eyes and dry mouth, parotid gland enlargement, or unexplained dental caries in the setting of abnormal serologic tests, there can be a significant overlap of symptoms with RA and SLE.

This study highlights the difficulty in diagnosing primary SS, due in part to the absence of gold-standard tests and leading to the use of classification systems instead. Dr Astrid Rasmussen, MD, PhD, of the Oklahoma Medical Research Foundation in Oklahoma City and colleagues sought to identify the overlapping clinical and serologic features that may be associated with a misdiagnosis of RA, SLE, or SSc in patients with primary SS, as these features have the potential to delay or confound the diagnosis of SS.  

The study included 1175 participants with symptomatic dry eyes and dry mouth (sicca); of these, 524 (44.6%) had reported a history of previously diagnosed or suspected RA (n=191), SLE (n=146), or SSc (n=29). Among those with 2 or more diagnoses (n=158), the most commonly occurring combination was SLE and RA (n=89). 

The investigators reviewed the patients’ past medical records and lab results to assess prior diagnoses of RA,  SLE, or  SSc. Additional testing was obtained to rule out or confirm these prior diagnoses. Participants were evaluated and classified as having SS using the American-European Consensus Group Criteria.

Of the 524 participants responding “yes” or “unsure” as to whether they had ever been diagnosed with RA, SLE, or SSc, 24.5% (n=130) had criteria confirmed for 1 or more non-SS autoimmune disease. In 75.2% (n=394), the previous autoimmune disease diagnosis was excluded; in this group, 46.5% (183 subjects) met criteria for primary SS.

When the researchers examined the serologic characteristics of participants with and without prior diagnoses, a positive ANA serology was found in 128 of 146 participants with a prior diagnosis of SLE, compared to 622 out of 881 participants without the diagnosis (P=8.77E-06). A positive RF serology was found in 70 of 191 participants with a prior diagnosis of RA, compared with 445 of 845 participants without the diagnosis (P=3.38E-05).

Participants with a previous diagnosis of SLE were likely to be younger (52 vs 56 years, P=.0003) and female (P=.017) whereas participants with a previous diagnosis of RA  were more likely to older (58 vs 54 years, P=5.89E-06) and not Caucasian (P=.03). 

Interestingly, a previous diagnosis of a non-SS autoimmune disease was not predictive of meeting criteria for SS and did not lead to a significant delay in an SS diagnosis, compared with those not suspected of having other autoimmune diseases (7.15 vs 5.91 years, respectively, P=.289).

Summary and Clinical Applicability

This observational study demonstrated that in a cohort of patients with symptoms of sicca, overlapping serological abnormalities may have led to an erroneous diagnosis of the autoimmune diseases SLE, RA, or SSc prior to a final, revised diagnosis of primary SS. However, no significant delay in diagnosis of primary SS was found in this group of patients.

The authors write, “In our cohort of patients with sicca, we identified a significant proportion of subjects eventually classified as [primary] pSS who had been told they had RA, SLE, SSc or two or more other diseases. Serological abnormalities, namely the presence of ANAs and/or RF, seem to be the drivers of such misdiagnoses.”

These results have the potential to be clinically applicable because an accurate diagnosis is essential in guiding treatment and prognosis. 

Limitations and Disclosures

The authors acknowledge, “We have assumed that the previous diagnoses were erroneous, but it is possible that a few subjects had either RA or SLE at a previous point that was not documented in the available medical records, and that at the time of our evaluation they were best classified as [primary] SS”.

One study author disclosed receiving consultant fees from UCB and honoraria from Lilly. Research was funded by the National Institutes of Health, the Oklahoma Medical Research Foundation, the Phileona Foundation, and the Sjogren Syndrome Foundation.

Reference

Rasmussen A, Radfar L, Lewis D, et al. Previous diagnosis of Sjögren’s Syndrome as rheumatoid arthritis or systemic lupus erythematosus [published online ahead of print March 21, 2016]. Rheumatology (Oxford). 2016; doi:10.1093/rheumatology/kew023.