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Current State of Sjögren’s Disease: Expert Answers to Your Commonly Asked Questions

Released: May 23, 2026

Thomas Grader-Beck
Thomas Grader-Beck, MD
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Key Takeaways
  • Unexplained neuropathy and renal tubular acidosis are atypical symptoms of Sjögren’s disease that are commonly overlooked by HCPs.
  • Although lip biopsy and autoantibody detection are key diagnostic tools, emerging therapies will need to be studied to determine their efficacy in those with anti-Ro/SSA–negative disease.
  • Approximately one half of patients with small fiber neuropathy are misdiagnosed with fibromyalgia; therefore, HCPs must consider the inflammatory nature of patients’ Sjögren’s disease symptoms.

In this commentary, Thomas Grader-Beck, MD, answers questions posed by healthcare professionals (HCPs) during a series of live presentations titled, “Sjögren’s Myth Busters: Can You Detect Fact From Fiction on Emerging Therapies?” that were held in February through April 2026. Learn how to address persistent gaps in Sjögren’s disease care, including key considerations for assessing disease activity, correctly diagnosing comorbid fibromyalgia, and understanding the systemic symptoms that influence prognosis.

What atypical symptoms are commonly missed in patients with Sjögren’s disease?
HCPs may overlook Sjögren’s disease in patients presenting with otherwise unexplained neuropathy. This is particularly true in patients with small fiber neuropathy or autonomic dysfunction, where Sjögren’s disease initially may not be considered in the differential diagnosis. In these cases, serologic testing for anti-Ro/SSA is recommended, along with functional testing of tear and salivary flow, as an initial step. If significant impairment is detected in the absence of autoantibodies, a minor salivary gland biopsy should be considered, as neuropathies are frequently observed in seronegative patients with Sjögren’s disease.

Another manifestation that may be easily overlooked by HCPs is renal tubular acidosis (RTA). This is especially true in patients with incomplete RTA, who may present with hypokalemia despite the absence of overt metabolic acidosis. Symptoms are often nonspecific and may include fatigue, muscle weakness, nephrolithiasis, or intermittent electrolyte abnormalities.

When should persistent fatigue trigger HCPs to reassess patients’ disease activity?
The short answer is when patients report persistent fatigue, new disease-related manifestations should be considered and evaluated. One example is screening for pulmonary involvement, which may remain clinically unrecognized for prolonged periods of time in Sjögren’s disease. According to current consensus guidelines, a chest x-ray is advised for all patients with Sjögren’s disease. In clinical practice, however, high-resolution chest CT is often the preferred imaging modality in patients with suspected pulmonary involvement because of its greater sensitivity for detecting early or otherwise subclinical interstitial lung abnormalities and small airway disease. Pulmonary function tests should accompany imaging evaluation, as they may help identify physiologic abnormalities even in patients with minimal respiratory symptoms. Of course, the list of potential disease manifestations is broad, and evaluation for unrelated but potentially contributing conditions such as sleep apnea, hypothyroidism, anemia, or medication-related fatigue should also be considered.

How do you evaluate patients who are anti-Ro/SSA autoantibody negative?
In patients with suspected Sjögren’s disease, the primary diagnostic evaluation includes serologic testing and assessment for objective glandular dysfunction. In patients with anti-Ro/SSA–negative disease, testing for anticentromere antibodies can also be considered, as this may identify an additional subset of patients with Sjögren’s disease. Minor salivary gland biopsy is recommended in seronegative patients, and according to current classification criteria, biopsy interpretation should include standardized focus score assessment. A focus score should be reported typically as a numeric value with a decimal, reflecting the relationship between the number of lymphocytic foci and the measured glandular tissue surface area. Unfortunately, many biopsies are still interpreted incorrectly by pathologists, which can create substantial confusion for both patients and HCPs.

Seronegative patients can still present with many of the same systemic manifestations observed in seropositive patients, although these manifestations may occur somewhat less frequently overall. By contrast, neurologic manifestations may be relatively enriched among seronegative patients.

At present, there are limited data regarding the efficacy and safety of emerging therapies in anti-Ro/SSA–negative Sjögren’s disease, which makes individualized clinical assessment especially important. I would also discourage the use of the Early Sjögren’s Syndrome Panel, as it has not demonstrated meaningful clinical utility in my practice.

What can best distinguish systemic disease activity from comorbid fibromyalgia?
One of the first considerations should be evaluation for small fiber neuropathy. Studies have suggested that a substantial proportion of patients with small fiber neuropathy are initially misdiagnosed with fibromyalgia. Evaluation should include a careful neurologic examination assessing temperature sensation, pinprick sensation, and other sensory abnormalities, with skin biopsy considered when clinically appropriate.

The character of pain may also provide important clinical clues. Patients with fibromyalgia often describe diffuse widespread pain and sensory hypersensitivity that differs qualitatively from inflammatory joint pain or myalgia related to systemic autoimmune disease. However, there is unfortunately no single diagnostic test that can reliably distinguish systemic Sjögren’s disease from comorbid fibromyalgia, and evaluation often depends on careful assessment of the specific manifestations involved.

When inflammatory joint pain remains uncertain, musculoskeletal ultrasound or MRI can be helpful in identifying objective evidence of synovitis or other inflammatory findings. Ultimately, distinguishing systemic Sjögren’s disease activity from fibromyalgia requires integration of the clinical history, examination findings, imaging studies, and exclusion of other contributing processes.

How do systemic symptoms of Sjögren’s disease influence patients’ long-term prognosis?
In general, the burden of systemic immune-mediated disease activity correlates with an increased risk of organ involvement and lymphoma. At the same time, there are no data suggesting that any single symptom domain alone definitively predicts the overall burden of systemic disease. This is similar to many other immune-mediated rheumatic diseases, where the cumulative burden and pattern of inflammation over time often have greater prognostic significance than any isolated manifestation.

If systemic immune activity remains unrecognized or insufficiently controlled, chronic inflammation may contribute to progressive organ dysfunction, cardiovascular risk, and lymphoma development in susceptible patients.

Even relatively indolent processes, such as mucosa-associated lymphoid tissue lymphoma, can still substantially contribute to long-term morbidity and mortality. More effective therapies capable of modifying disease progression are still needed for these patients. This does not necessarily mean that disease-modifying antirheumatic disease therapy is appropriate for every patient. However, in selected individuals with significant systemic disease activity, earlier immunomodulatory intervention may warrant consideration in an effort to reduce ongoing pathogenic immune activation and limit long-term organ damage.

How do the ESSDAI and ESSPRI complement each other when assessing disease burden?
The EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) measures the systemic disease activity of Sjögren’s disease, whereas the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) evaluates patients’ subjective symptom burden. Both tools are important in clinical practice because they capture different aspects of the disease experience. Many patients may have relatively limited systemic disease activity by ESSDAI criteria but still experience substantial fatigue, pain, or dryness symptoms that significantly affect quality of life.

At present, use of both ESSDAI and ESPRI is recommended for clinical practice. Since disease manifestations are often stable over time in a given patient, it does not take long to complete an ESSDAI (eg, 1 minute or less). Ideally, future assessment tools would better integrate systemic disease activity and patient-reported symptom burden into a more unified and clinically meaningful measure of disease impact.

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