Despite being one of the most common autoimmune diseases, Sjögren’s is often missed or misdiagnosed…

Dry eyes and dry mouth are common complaints and most are not caused by Sjögren’s disease, which is part of what makes the condition easy to miss.

Sjögren’s disease is a systemic autoimmune condition that particularly affects the salivary and tear glands. The textbook picture is persistent dry eyes and dry mouth, but patients may also present with fatigue, joint pain, recurrent salivary gland swelling or potentially serious manifestations involving the lungs, kidneys, skin or nervous system. Challengingly, some people have little or no obvious dryness when more systemic features first emerge. Sjögren’s disease usually presents in females around 40s to 50s.

That variability matters. Sjögren’s can significantly affect quality of life and, in a subset of patients, is associated with serious complications including organ involvement and lymphoma. The challenge is not to investigate every patient with dry eyes, but to recognise when the overall pattern deserves a closer look.

Evaluating dryness

Dryness symptoms are common, and careful evaluation to look for underlying causes is key. Dry eyes (xerophthalmia) may be caused by excessive screen time, contact lenses or ageing. Dry mouth (xerostomia) may be caused by diabetes, medications or anxiety. Dry eyes may manifest as gritty or burning eyes, and dry mouth may manifest with difficulty swallowing, or early and severe dental disease. Not every patient will volunteer these symptoms and may need to be asked specifically.

Consider Sjögren’s if the sicca is unexplained after evaluation, particularly when accompanied by the other cardinal signs including fatigue, arthralgias and possibly organ disease.

Sometimes dryness symptoms may appear after organ manifestations, so the absence of dryness does not rule out Sjögren’s disease.

Testing for Sjögren’s disease

There is no single test to diagnose Sjögren’s disease, and it is important to investigate mimics such as diabetes mellitus, and potential organ involvement, as guided by the clinical evaluation.

Autoimmune serology may be helpful. Antinuclear antibody (ANA) positivity can be seen in around 80% of cases. Likewise, anti-Ro60/TROVE2 and anti-Ro52/TRIM21 serum autoantibodies (previously known as anti-SSA/Ro) may be positive in up to 70-80% of individuals.

Anti-Ro52/TRIM21 and anti-Ro60/TROVE2 antibodies are an important part of the internationally recognised ACR/EULAR classification criteria, while ANA, anti-SSB/La and rheumatoid factor can provide additional information. Rheumatoid factor can be positive in approximately 50% of Sjögren’s patients but lacks diagnostic specificity.

Serology needs to be interpreted in context. A positive autoantibody does not automatically mean a patient has Sjögren’s, and negative serology does not necessarily exclude it. Around a quarter of patients may lack the classic serological markers, so if the index of suspicion for Sjögren’s remains high, they should be further referred for evaluation.

Additional investigations could be considered, including salivary gland imaging (ultrasound) and objective measures of sicca (e.g., Schirmer’s test).

When to refer?

In Australia, and depending on the location, a referral to a rheumatologist or clinical immunologist should be considered after the initial evaluation for the work-up or confirmation of Sjögren’s disease.

Below is a list of referral prompts, although they are by no means an exhaustive or definitive list:

• Persistent and unexplained sicca
• Positive Sjögren’s-related serology, particularly anti-Ro60/TROVE2 and/or anti-Ro52/TRIM21
• Recurrent and unexplained salivary gland swelling
• A combination of sicca, arthralgias and/or fatigue

Specialist assessment may involve objective testing of tear or salivary function, further immunological investigation and, in selected patients, a minor salivary gland biopsy.

Some features warrant particular attention. Persistent salivary gland enlargement, lymphadenopathy, unexplained weight loss, and palpable purpura have been associated with a higher risk of lymphoproliferative disease in Sjögren’s and should warrant further and prompt assessment.

Management

For many patients, the burden of Sjögren’s is not captured by test results or an official diagnosis.

Dryness can affect eating, speaking, sleeping, dental health and everyday comfort. Fatigue and pain can also be particularly disabling, and can affect occupation, daily function, and socialisation. Management often involves several disciplines, including primary care, clinical immunology or rheumatology, ophthalmology, oral medicine and dentistry.

Globally, there is currently no approved disease-modifying therapy that treats Sjögren’s as a whole, so much of care remains directed towards relieving dryness, protecting the eyes and teeth, managing pain and fatigue, and treating specific systemic manifestations when they occur. Targeted treatments are advancing through clinical development, however, reflecting a growing understanding of the immune pathways involved in the disease.

Ongoing care

Monitoring and follow-up in GP can support effective symptom management, and reduce the risk of complications. This includes:

• reviewing medicines that may worsen dryness
• oral and eye care through encouraging regular dental visits (at least 6 -monthly) and lubricating eye drops
• monitoring for new systemic symptoms
• ensuring patients remain connected with the appropriate specialist services;
• monitoring overall health and function
• consider referring patients to patient support groups such as Sjögren’s Australia

Although Sjögren’s may be clinically stable for some, it is important to be on the lookout for complications that arise such as lymphoma, which occurs in 5-10% of patients with Sjögren’s.

Moving towards more precise Sjögren’s care

One reason Sjögren’s remains difficult to diagnose and manage is that it is not the same disease in every patient. Globally, efforts are being made to better understand the pathophysiology and risk factors for the development of this disease. This will lead to the development of new biomarkers for the diagnosis and prognosis in Sjögren’s, as well as targeted therapies.

The aim is to move towards a future where we can better identify which patients are likely to remain relatively stable, which may be at greater risk of systemic complications, and eventually which treatments are most likely to help them. That work is still developing, and emerging biomarkers are not yet substitutes for established clinical assessment. For GPs today, however, earlier recognition remains one of the most useful contributions we can make.

Key takeaways

• Think beyond dry eyes and dry mouth: Sjögren’s is a systemic autoimmune disease and may present with fatigue, joint symptoms, gland swelling or organ involvement
• Look for a pattern: persistent unexplained sicca combined with other autoimmune or systemic features should raise suspicion
• Blood tests are helpful, but not definitive: negative serology does not exclude Sjögren’s when clinical suspicion remains high
• Consider referral when the picture does not add up: objective tear and saliva testing and, in some patients, salivary gland biopsy may be needed
• Ongoing care matters: GPs can play an important role in symptom management, oral and eye health, and recognising new systemic complications

More information

Sjögren’s Australia

Lee AYS, Rischmueller M. The diagnosis and misdiagnosis of Sjögren disease. Internal Medicine Journal. 2024;54:833-835. doi: 10.1111/imj.16395

Price EJ et al. British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease. Rheumatology. 2025;64:409-439. doi: 10.1093/rheumatology/keae152

Shiboski CH et al. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren’s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts. Arthritis Rheumatol. 2017;69:35-45. doi: 10.1002/art.39859

Hoi A, Lee AYS, Marshall G, Kirana C, Rischmueller M. Sjögren’s disease in Australia: why we need to pay attention. MJA InSight+. 2025

Dr Adrian Lee (MBBS BMedSc(Hons) PhD FRACP FRCPA AFRACMA) is a Clinical Immunologist at Westmead Hospital and ICPMR, Post-Doctoral Researcher at The Westmead Institute for Medical Research, and Clinical Senior Lecturer in the Faculty of Medicine and Health at the University of Sydney. His clinical and research foci are in autoimmunity, autoantibodies, B cells and Sjögren’s disease.