Diagnostic Value of Lip Mucosal Impression Cytology and <i>in vivo</i> Confocal Microscopy in Primary Sjogren's Syndrome

Abstract

Background: Labial gland biopsies play a significant role in diagnosing primary Sjogren's syndrome (pSS) but their clinical use is limited because of their invasiveness. We assessed the value of impression cytology (IC) and in vivo confocal microscopy (IVCM) for diagnosing pSS. Methods: Consecutive patients with clinically suspected pSS (n = 102) were enrolled. According to the American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) criteria, all patients underwent labial gland biopsies, serum anti-Sjogren's syndrome A (SSA)/Ro antibody testing, Schirmer's tests (STs), corneal staining and unstimulated whole saliva flow (UWS) determinations. The patients were divided into pSS (n = 28) and control (n = 74) groups, all underwent lip mucosa IC and IVCM analyses. The salivary gland ultrasonography (SGUS) score, ocular surface disease index (OSDI), tear meniscus height (TMH), tear film breakup time (BUT), and meibomian gland score were recorded. The associations between IC/IVCM parameters and clinical/laboratory results were analyzed. Findings: The absolute agreements between lip mucosal IC and the ACR-EULAR criteria (98·04%)/ labial gland biopsy (97·06%) were good. A combination of IC and anti-SSA/Ro antibody determination showed high predictive value for diagnosing pSS. Compared with controls, IVCM revealed significant lip mucosal epithelium thinning and lamina propria atrophy in the pSS group (both, P < 0·001). The sensitivities for diagnosing pSS corresponding to a lamina propria thickness ≤126 μm and a gland diameter ≤90 μm were both 85·71%; the specificities were 90·54% and 100%, respectively. A combination of IVCM results and anti-SSA/Ro antibody results showed high predictive value for diagnosing pSS. Interpretation: Characteristic cellular and morphological changes of lip mucosa in patients with pSS could be detected by IC and IVCM. These noninvasive and easy-to-perform examinations may be an alternative to labial gland biopsies for diagnosing pSS. Funding Statement: This study was supported by a grant from the Beijing Health and Family Planning Commission, Capital’s Funds for Health Improvement and Research [Grant numbers: CFH2018-2-4093]. Declaration of Interests: The authors state: None of the authors have any conflicts of interest to report. Ethics Approval Statement: The study was performed according to the principles of the Declaration of Helsinki and was approved by the Human Research and Ethics Committee, Peking University Third Hospital; written informed consent was obtained from each study participant.