Demographics (age, sex), reasons for ordering the SGU, prior and final diagnoses, clinical data (including extraglandular involvement, recurrent parotid swelling and lymphoma), SGU results and grading (when available), as well as other diagnosis procedures such as the Schirmer test, an SG biopsy and scintigraphy were collected from the electronic clinical history. The laboratory data collected included the presence of autoantibodies (ANA, Anti-SSA, Anti-SSB and RF), complement levels (C3 and C4) and cryoglobulinemia (Table 1).

Diagnosis of SS (primary (pSS) or secondary (sSS)), was carried out by the responsible rheumatologist. We confirmed whether or not those patients diagnosed with pSS fulfilled the 2002 or the 2016 American-European classification criteria by reviewing their electronic clinical histories.8,9

Extra glandular involvement was considered present based on the following parameters: articular (arthralgia, arthritis), renal (nephritic syndrome or renal tubular acidosis), peripheral nervous system (inflammatory demyelinating polyneuropathy, vasculitis, or pure sensory axonal polyneuropathy), neurological (cerebrovascular stroke, optic neuritis, seizures, cerebral vasculitis, or multiple sclerosis-like syndrome) and pulmonary (interstitial lymphocytic pneumonitis).

Three expert rheumatologists in SGU performed a standardized SGU assessment by utilizing a real-time, high-resolution ultrasound machine (EsaoteMyLab™X8 Platform Ultrasound System). The assessment was performed on B mode with a linear transducer (frequency from 7.5 to 15MHz and gain from 35 to 50dB) and Doppler mode was applied when needed.

The patients were assessed lying on the bed in a supine position with the neck slightly extended and turned away from the assessed side. Both the parotid and submandibular glands were assessed; the submandibular glands were assessed only in the longitudinal scan, while the parotid glands were assessed in both the longitudinal and transverse scans.

Based on all of the possible glandular aspects assessed with US (hyperechoic lines, number and size of hypoechoic images, etc.), we evaluated only parenchymal homogeneity for diagnostic purposes in accordance with the available literature.10 These findings were graded based in the experience of the authors with a 4 grades semiquantitative score, quite similar to the proposed by OMERACT group in 20192 that considers parenchymal homogeneity ranging from 0 to 3 and can be assessed in both parotid (Fig. 1) and submandibular (Fig. 2) glands. The definition of each grade is specified below: Grade 0: homogeneous normal glandular parenchyma; grade I: minimal glandular heterogeneity without hypoechoic images; grade II: moderate parenchymal heterogeneity with hypoechoic images; grade III: severe heterogeneity with hypoechoic lesions in the entire glandular parenchyma.

Fig. 1.

Parotid longitudinal scan assessment. Grade 0 (A), grade I (B), grade II (C), grade III (D).

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Fig. 2.

Submandibular longitudinal scan assessment. Grade 0 (A), grade I (B), grade II (C), grade III (D).

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We determined the autoimmunity status from the electronic clinical history. ANA were considered positive when >1:80, as measured by indirect immunofluorescence of cryostat sections from rat tissues (kidney, liver, and stomach) and in cultured HEp-2 cells (MarDx Diagnostics, Carlsbad, CA, USA) using a fluorescein-conjugated rabbit antihuman antibody (DAKO, Copenhagen, Denmark) according to standard procedures. RF (positive at >20IU/mL) was measured by laser nephelometry (Beckman Coulter, Brea, CA, USA). Anti-SSA and anti-SSB antibodies were detected using an enzyme-linked immunosorbent assay (Rheuma ELISATM System; Whittaker Bioproducts, Walkersville, MD, USA).

Based on the SGU results, we calculated the positive predictive value, negative predictive value, sensitivity and specificity of the test. We also compared patients who fulfilled any classification criteria (the 2002 American-European Consensus Group (AECG) criteria or the 2016 ACR/EULAR criteria) with those who had been only clinically diagnosed with Sjögren's syndrome.

Finally, for in-patients who fulfilled any of the classification criteria (2002 AECG or the 2016 ACR/EULAR criteria) we compared clinical and laboratory characteristics, comparing those who presented either pathological or normal SGU findings.

This study was approved by the ethics committee for drug research at the Hospital General Universitario Gregorio Marañon.

We used IBM® SPSS® Statistics 25 for the statistical analysis. Quantitative measures are expressed as the mean, range, and standard deviation. Categorical measures are expressed as the absolute frequency and percentage. We also calculated the sensitivity and specificity of the SGU in our cohort. Finally, we compared groups by using the Student's T-test and the Chi-squared test and Fisher test when applicable.

Ultrasound findings were pathological in 23 patients (13.1%), 20 of them (87%) women. In addition, 34% of cases had no previous diagnosis, while the most common previous diagnoses were pSS (39.1%), rheumatoid arthritis (21.7%) and SLE (4%).

Only one patient with sicca syndrome but with antibodies and sialography that were not compatible, had a pathological SGU but did not fulfilled any diagnosis criteria; also no biopsy was made.

After the diagnostic exercise, of the 23 cases with pathological SGU, 17 (73.9%) were diagnosed with pSS and 5 (21%) with sSS, with only one patient presenting abnormalities in the SGU assessment.

There were 45 patients clinically diagnosed with SS by the treating rheumatologist and 34 of them also fulfilled the SS classification criteria, being 27 pSS (12 cases with previous diagnosis and 15 with new diagnosis) and 7 sSS (all new diagnoses, 4 of them with RA and 3 with SLE) (Table 2).

Of the 27 cases of pSS, the ultrasound was pathological in 59.3%, all meeting the 2002 classification criteria, while 20 (76%) met the 2016 criteria, and 6 of them (22%) presented recurrent parotitis.

About extra-glandular manifestations, the most common was arthritis (7.4%) and there were no lymphoma cases reported.

Regarding the other diagnostic tests, Schirmer test was pathological in about 94% of the patients in whom it was performed (18/19), scintigraphy was positive in about 83% (15/18), and finally, of the 6 biopsies performed, 50% were pathological.

Of the 102 assessments as part of the diagnostic work-out for SS, 74% were ANA positive, 77.8% anti-Ro positive, 44% anti-LA positive, 48% RF positive, 3.7% positive for cryoglobulins. 36% also presented hypocomplementemia for C3 and 28% for C4.

Sensitivity and specificity were 48% and 98% respectively, with a positive predictive value of 95% and a negative predictive value of 70%.