Introduction and background

Sjögren's disease (SjD), historically termed Sjögren's syndrome, is a chronic autoimmune disorder characterized by lymphocytic infiltration of the lacrimal and salivary glands, producing the hallmark sicca complex of keratoconjunctivitis sicca and xerostomia [1,2]. This review focuses on primary SjD, the prototypic form of the disease, unless otherwise specified. SjD is no longer regarded as a localized "sicca syndrome" but rather as a systemic autoimmune disease capable of affecting nearly every organ system, including the lungs (interstitial lung disease), kidneys (tubulointerstitial nephritis), peripheral and central nervous systems, and the hematologic system, where it confers a markedly increased risk of non-Hodgkin lymphoma compared with the general population [2,3]. In 2025, an international Delphi consensus process formally recommended replacing the term "Sjögren's syndrome" with "Sjögren's disease," recognizing it as a distinct systemic autoimmune disease and discouraging the routine use of the historical primary/secondary classification [1].

Despite its systemic burden, SjD remains profoundly underdiagnosed and undertreated. Population-based and cross-sectional cohort data indicate diagnostic delays averaging approximately five to six years from symptom onset, with a reported mean diagnostic latency of 5.98 years (median two years) in a German cohort. Longer delays correlate with worse self-reported general health and greater symptom burden, including gastrointestinal symptoms and vaginal dryness [4]. Earlier population-based data from Taiwan similarly demonstrated a substantial lag between onset of sicca symptoms and formal diagnosis using national insurance claims data [5]. This “diagnostic odyssey” is compounded by the heterogeneity of clinical presentation, frequent overlap with other connective tissue diseases, and the historically narrow framing of SjD as predominantly a glandular or ophthalmologic condition rather than a multisystem disease [4-6].

A second, equally consequential unmet need is therapeutic: despite decades of clinical investigation, no biologic or systemic disease-modifying antirheumatic drug (DMARD) has received regulatory approval for SjD, and management continues to rely on symptomatic measures such as artificial tears, punctal plugs, sialogogues (pilocarpine, cevimeline), and hydroxychloroquine, none of which have been convincingly shown to alter systemic disease trajectory [3,7]. The 2020 European Alliance of Associations for Rheumatology (EULAR) recommendations for the management of Sjögren's syndrome with topical and systemic therapies reflect this gap, providing predominantly low- to moderate-grade evidence for symptomatic interventions and reserving systemic immunosuppression and biologic agents for organ-threatening extraglandular manifestations on a largely off-label basis [7]. The 2025 British Society for Rheumatology guideline on the management of adult and juvenile-onset Sjögren disease likewise underscores the paucity of high-quality, disease-modifying evidence and the heavy reliance on extrapolation from other autoimmune diseases [8].

This review aims to (1) characterize the principal unmet needs in SjD across diagnostic, symptomatic, and therapeutic domains; (2) clarify the clinimetric role and practical utility of the ESSDAI and ESSPRI instruments in clinical trials and routine practice; and (3) summarize the maturing late-stage therapeutic pipeline, providing practicing rheumatologists with a framework for navigating the transition from purely symptomatic management toward targeted, immunoselective biologic therapies.

Relevant English-language publications were identified through PubMed/MEDLINE, Embase, and Google Scholar through June 2026, with emphasis on recent guidelines, clinical trials, systematic reviews, and landmark studies related to SjD.