Ultrasound-guided core needle biopsy and incisional biopsy of the parotid gland are comparable in diagnosis of primary Sjögren's syndrome.

OBJECTIVES: Salivary gland lymphocytic infiltrates are a hallmark of primary SS (pSS), but traditional biopsy techniques hold several disadvantages. Ultrasound-guided core needle (US-guided CN) parotid gland biopsy is minimally invasive and reliable for diagnosis of lymphoma in pSS. This proof-of-concept study aimed to explore this technique in the diagnostic work-up of pSS and is the first to address its value in a consecutive cohort independently of the presence of salivary gland swelling. METHODS: Combined incisional and US-guided CN parotid biopsy was performed in 20 patients with suspected or confirmed pSS from the Belgian Sjögren's Syndrome Transition Trial (BeSSTT). Surface area and presence of a focus score (FS) of at least one, germinal centres and lymphoepithelial lesions were recorded. RESULTS: Salivary gland tissue was interpretable in 19 patients. Fourteen patients had ≥4 mm2 salivary gland tissue by both techniques, in four US-guided CN biopsies salivary gland tissue was <4 mm2. Paired biopsies ≥4 mm2 displayed a concordance of 90% for FS ≥ 1. Presence of lymphoepithelial lesions and germinal centres showed absolute concordance. Of four US-guided CN biopsies <4 mm2, three interpretable incisional biopsies were available, 2/3 with perfect concordance. When including biopsies of <4 mm2 salivary gland tissue, presence of FS ≥ 1 or germinal centres gave a sensitivity of 70% in incisional and of 69% in US-guided CN biopsy. CONCLUSIONS: US-guided CN biopsy of the parotid gland is at least equivalent to incisional biopsy of the parotid gland in the diagnostic work-up of pSS.

The value of separate detection of anti-Ro52, anti-Ro60 and anti-SSB/La reactivities in relation to diagnosis and phenotypes in primary Sjögren's syndrome.

OBJECTIVES: Autoantibody detection is an essential step in pSS diagnosis. However, the value of separate anti-Ro52, anti-Ro60 and anti-SSB/La detection in pSS diagnosis and phenotyping has not been extensively studied. This study aimed to explore disease characteristics of anti-SSA/Ro positive, suspected and definite pSS patients, in relation to serological profiles based on anti-Ro52, anti-Ro60 and anti-SSB/La reactivity. METHODS: Of 187 anti-SSA/Ro positive patients included in the Belgian Sjögren's Syndrome Transition Trial (BeSSTT), 155 were considered definite pSS patients, due to fulfilment of the 2016 ACR-EULAR classification criteria, and 32 suspected, due to reactivity against SSA/Ro without presence of other criteria. None of the patients met any of the ACR-EULAR exclusion criteria for pSS. Patients were grouped based on the presence of anti-Ro52, anti-Ro60 and anti-SSB/La antibodies. RESULTS: Mono-reactivity against Ro60 or Ro52, double reactivity against Ro52/Ro60 and triple reactivity against Ro52/Ro60 and SSB was detected in respectively 30, 23, 70 and 60 patients. Mono-anti-Ro60 positive patients showed the least pSS features. Mono-anti-Ro52 positive patients reported a significantly higher dryness burden (p=0.016) and tended toward more salivary gland ultrasound (SGUS) abnormalities (p=0.054) than mono-anti-Ro60 positives. Double positive patients showed similar characteristics as mono-anti-Ro52 positive patients, whereas triple positive patients showed lowest unstimulated salivary flow rates (p=0.002) and Schirmer tests (p=0.002), highest ocular staining scores (p<0.001), most positive labial salivary gland biopsies (p=0.039), most laboratory abnormalities compatible with B-cell hyperactivity and highest SGUS scores (p<0.001) compared to other patient groups. CONCLUSIONS: These data indicate that separate detection of anti-Ro52, anti-Ro60 and anti-SSB/La reactivity is not only relevant towards pSS diagnosis, but markedly aids in patient stratification and evaluation of disease burden. Our results suggest a stepwise model in which mono-reactivity against Ro60 displayed the least objective and subjective glandular pSS features, whereas glandular abnormalities and signs of B-cell hyperactivity were most present in patients showing triple reactivity against Ro60, Ro52 and SSB/La.

Discriminative power of salivary gland ultrasound in relation to symptom-based endotypes in suspected and definite primary Sjögren's Syndrome.

OBJECTIVES: Salivary gland ultrasound (SGUS) is emerging as essential tool in primary Sjögren's Syndrome (pSS), but its link to symptom-based endotypes is unknown. Therefore, we explored SGUS outcomes in relation to endotypes in patients with definite and suspected pSS. METHODS: Definite pSS patients (n = 171) fulfilling the 2016 ACR/EULAR classification criteria, and suspected pSS patients (n = 119), positive for at least one criterion, were included in the Belgian Sjögren's Syndrome Transition Trial (BeSSTT). Stratification into endotypes according to the Newcastle Sjögren's Stratification Tool resulted in low symptom burden (LSB), pain dominant with fatigue (PDF), dryness dominant with fatigue (DDF) and high symptom burden (HSB). SGUS was assessed with Hocevar score (0-48). The dataset was randomly divided into a discovery (n = 203) and replication (n = 87) cohort. RESULTS: SGUS had strong discriminative power for pSS classification (AUC=0.74), especially in DDF (AUC=0.89). In definite pSS, Hocevar scores in DDF were high compared to other endotypes (38 (20-44) versus 18 (9-33); p < 0.001). Patients with highest SGUS-scores showed more sicca and laboratory abnormalities. Moreover, a subset of young, anti-SSA/Ro positive patients not fulfilling classification criteria showed clear SGUS abnormalities. Replication showed similar results. CONCLUSIONS: SGUS-scores were significantly higher in definite pSS with DDF endotype, providing the first evidence of imaging abnormalities in salivary glands matching distinct biological profiles ascribed to pSS endotypes. Additionally, a subset of patients with potential early disease was detected based on presence of anti-SSA antibodies and high SGUS-scores. These results underscore the role of SGUS as powerful tool both in pSS classification and stratification.