Sjögren's disease

• 1. Introduction

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  Fatigue, not dryness, topped the list when Sjögren's disease patients were described in a 2021 article. Fatigue was named by 79%, dry eyes by 75% and dry mouth by 73%. Joint pain followed at 65%, trouble sleeping at 64%, eye discomfort at 60%, muscle pain at 56% and brain fog at 54%. A majority said each of these eight symptoms had a major or moderate effect on their lives.

  Sjögren's disease, abbreviated SjD, was formerly called Sjögren syndrome. It is a long-term autoimmune disease, meaning the immune system turns on the body's own tissue. Its main targets are the exocrine glands, especially the lacrimal glands that make tears and the salivary glands that make saliva.

  This documentary asks why a condition with such a heavy toll can go unrecognized for years. It asks what sets the immune system off, who is most likely to be affected, and how doctors confirm the disease. It also asks what can be done once the answer is yes.

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• 2. Beyond Dryness

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  A chronic cough and numbness in the arms and legs are among the less familiar signs that can accompany the hallmark dry mouth and dry eyes. Dry skin, a dry nose and vaginal dryness may also appear, along with thyroid problems and muscle and joint pains. Some skin dryness comes from immune cells called lymphocytes invading the skin's glands. The disease can reach well past the surface. The kidneys, blood vessels, lungs, liver, pancreas and brain can all be affected.

  Severity varies enormously. Some people have only mild dry eyes and a dry mouth, and many can manage their problems by treating the symptoms. Others develop blurred vision, constant eye discomfort, recurrent mouth infections, swollen parotid glands, and difficulty swallowing and eating. Dysphonia, a term for vocal disorders including hoarseness, can also occur. As with other autoimmune diseases, symptoms may plateau, worsen or go into remission.

  Kidney involvement takes a specific form called autoimmune tubulointerstitial nephritis. It can bring proteinuria, which is excess protein in the urine, along with a urinary concentrating defect and distal renal tubular acidosis. Type I cryoglobulinemia is another known complication.

  Women carrying anti-Ro/SS-A and anti-La/SS-B antibodies face a higher rate of neonatal lupus erythematosus with congenital heart block when they become pregnant. That heart block can require a pacemaker.

  Celiac disease, fibromyalgia, lupus, autoimmune thyroiditis, multiple sclerosis and spondyloarthropathy all appear among the associated conditions. The disease can arise on its own or alongside another connective tissue disorder such as rheumatoid arthritis, lupus or systemic sclerosis. Non-Hodgkin lymphoma is the principal malignancy linked to it. Sjögren's is also described as the second most common cause of dysautonomia.

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• 3. A Slow Diagnosis

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  For several years, doctors often never consider Sjögren's disease at all. Dryness gets blamed on medications, a dry environment or aging, or it seems too minor to justify a deeper search. Dry eyes and dry mouth are common in people over 40, so many patients ignore them. Some medications cause similar symptoms. Patients also bring their complaints to different specialities, which scatters the clues. The disease has no specific, non-invasive diagnostic test.

  Blood tests are one step. Doctors look for antinuclear antibody and for rheumatoid factor. The typical patterns are anti-SSA/Ro and anti-SSB/La, and anti-SSB/La is far more specific. Anti-SSA/Ro turns up in many autoimmune conditions. Both tests are frequently negative in people who do have Sjögren's.

  Schirmer's test holds a strip of filter paper inside the lower eyelid for five minutes, then measures its wetness with a ruler. Less than 5 mm of liquid usually points to Sjögren's, though other eye conditions and medications shift the result. The rose bengal test instead places a nontoxic dye on the eye. Its distinctive colour reveals the state of the tear film and how fast tears evaporate. A slit-lamp examination can show dryness on the eye's surface.

  In an unstimulated saliva test, the person spits into a test tube every minute for about 15 minutes. Less than 1.5 ml counts as a positive result. A stimulated version has the person suck on a sugar-free sweet while collecting saliva. An unstimulated rate of 0.1 to 0.2 ml per minute, or a stimulated rate of 0.7 ml per minute or less, is abnormally low. Unstimulated saliva production falls by 40 to 70% between the ages of 20 and 80, but stimulated production is not affected.

  A lip biopsy removes a small tissue sample from the inner lip and examines it under a microscope for lymphocytes clustered around salivary glands. Its single most important result is the focus score, which counts clusters of at least 50 inflammatory cells in a 4 mm2 glandular section. The Chisholm-Mason grades are also widely used. Salivary gland ultrasound is non-invasive and may spare anti-SSA-negative patients an unnecessary biopsy. A sialogram, which injects a contrast agent into the parotid duct, looks for blockage and measures how much saliva flows.

  In 2016 an international group built on guidelines from the American College of Rheumatology and the European League Against Rheumatism to create the ACR-EULAR criteria. A person with previously reported dry eye or dry mouth symptoms has the disease if they score at least 4. A lip biopsy with a focus score of 1 or more earns 3 points, and so does a positive anti-SSA/Ro test. An ocular staining score of 5 or more, a Schirmer result under 5 mm, or an unstimulated saliva flow of 0.1 ml per minute or less each earn 1 point. Past head and neck radiation, active hepatitis C confirmed by a positive PCR test, AIDS, sarcoidosis, amyloidosis, graft-versus-host disease and IgG4-related disease can rule the diagnosis out.

  The criteria were designed mainly for recruiting people into clinical trials. A 2025 Swedish cohort study showed they were also effective for diagnosing patients.

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• 4. Immune Misfire

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  The first genome-wide association study of Sjögren's disease compared 395 patients of European ancestry with primary disease against 1,975 healthy controls. A replication study added 1,234 cases and 4,779 controls. The strongest signal came from the major histocompatibility complex region, which holds the human leukocyte antigen, or HLA, genes. Six other loci also showed associations: IRF5, STAT4, BLK, IL12A, TNIP1 and CXCR5.

  Ancestry changes which gene versions matter. Patients from Northern and Western Europe and North America show a high prevalence of the B8, DRw52 and DR3 genes. HLA-DR5 is related to Greek and Israeli patients. HLA class II alleles are tied to specific autoantibody subsets rather than to the disease itself. Positive anti-Ro and anti-La tests go with greater severity and a longer duration of disease.

  Hormones are a leading suspect for the imbalance between the sexes. Estrogen is considered one of the biggest factors behind differences in immune response between men and women, while androgens are generally thought to prevent autoimmunity. In mouse models, estrogen deficiency stimulated the presentation of autoantigens and induced Sjögren's-like symptoms. Another idea is microchimerism, in which fetal cells persist in a mother's circulation and may generate autoimmunity in women who have been pregnant.

  Epstein-Barr virus, hepatitis C and human T-lymphotropic virus 1 are among the most studied infectious agents. No direct cause-and-effect relationship has been identified. Epstein-Barr virus is present in the salivary glands of healthy people, but patients show a high rate of reactivation and increased levels of viral DNA. One proposed route is molecular mimicry, in which viral proteins resemble the body's own structures and confuse the immune system. Around 20 autoantibodies could be involved.

  The inflammation itself follows a proposed chain of events. Lymphocytes, including CD4+ T cells, B cells and plasma cells, infiltrate the salivary and lacrimal glands. Plasmacytoid dendritic cells gather early and produce high levels of type 1 interferons. Interferon alpha then pushes cells to make B-cell activating factor, known as BAFF, which drives abnormal B-cell maturation. The resulting self-reactive B cells make autoantibodies inside germinal centre-like structures, which are also where lymphoma is thought to originate.

  The picture is still incomplete. Researchers have found increased IL-1RA, an interleukin 1 antagonist, in cerebrospinal fluid, and it is associated with fatigue. Saliva shows the opposite pattern, with decreased IL-1ra, which could explain inflammation and dryness in the mouth.

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• 5. Who Is Affected

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  Nine out of 10 Sjögren's patients are women, and the disease is around 10 times more common in women than in men. Men are not spared, and primary Sjögren's in men tends to be a more severe form. A first-degree relative with an autoimmune disease and previous pregnancies are both identified risk factors. The role of race and ethnicity is unknown, and the disease has been reported in all areas of the world.

  Sjögren's disease is the third-most common rheumatic autoimmune disorder, behind rheumatoid arthritis and systemic lupus erythematosus. Between 0.2 and 1.2% of the population is affected, with half having the primary form and half the secondary form. Estimates in the United States run from 500,000 to 2 million people, and some reports suggest up to 3% of the population. A few studies put incidence at three to six per 100,000 per year.

  The average age of onset falls between 40 and 60, though any age can be affected. Prevalence generally increases with age. As many as half of all cases may be undiagnosed or unreported.

  Overlap with other conditions is large. Sjögren's is reported in 30-50% of people with rheumatoid arthritis and 10-25% of those with systemic lupus erythematosus.

  Shannon Boxx, a U.S. Olympic soccer player, has both Sjögren's disease and lupus. Tennis champion Venus Williams has been diagnosed with Sjögren's and said she had struggled with fatigue for years. Stephen McPhail, who played professional soccer for Ireland, Leeds and Cardiff City, was diagnosed with lymphoma and Sjögren's at age 29. The singer Halsey was diagnosed with Sjögren's alongside Ehlers-Danlos syndrome, mast cell activation syndrome and postural orthostatic tachycardia syndrome. The Serbian singer Slađana Milošević died after struggling with the disease.

  Singer-actress Carrie Ann Inaba serves as the US national awareness ambassador and spokesperson for the Sjögren's Foundation.

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• 6. Managing Symptoms

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  No treatment is known to restore gland secretion, so care is generally symptomatic and supportive. The goal is to ease each problem separately. Medications that can cause dryness, such as antihistamines, may also be stopped.

  For dry eyes, artificial tears are the starting point. Some patients with more severe problems wear goggles to raise local humidity. Others have punctal plugs inserted to keep tears on the surface of the eye longer. Cyclosporine, sold as Restasis, is prescribed for chronic dry eye because it suppresses the inflammation that disrupts tear secretion.

  For a dry mouth, sugar-free chewing gum, sips of water and saliva substitutes may be used. Prescription drugs can stimulate salivary flow, including cevimeline (Evoxac) and pilocarpine. Salagen is a manufactured form of pilocarpine that can help produce tears as well as saliva. Pilocarpine is derived from the jaborandi plant.

  Vaginal dryness, vulvodynia and painful intercourse are often reported by women with the disease. Personal lubricants are recommended to reduce irritation or pain.

  Ibuprofen and other nonsteroidal anti-inflammatory drugs can treat joint and muscle pain. Severe complications may call for corticosteroids, immunosuppressive drugs, intravenous immunoglobulins, or disease-modifying drugs such as methotrexate. Hydroxychloroquine, sold as Plaquenil, is generally considered safer than methotrexate. These drugs carry side effects including nausea, loss of appetite, dizziness, hair loss, stomach cramps, headache, liver toxicity and increased risk of infections. For systemic symptoms such as fatigue, joint pain, myositis and neuropathy, the biologic drugs rituximab and belimumab target B cells and have less toxic profiles than traditional immunosuppressive regimens.

  Dental care is often overlooked by patients. Without saliva, the mouth becomes an ideal setting for the bacteria that cause cavities. Treatment includes fluoride applied at home to strengthen enamel and frequent cleanings by a dental hygienist. Cavities that reach into the tooth cannot be treated by cleaning alone and can spread into the pulp, leading to extraction or root canal therapy. The same regimen is used for people whose salivary glands are damaged by head and neck radiation.

  No way to prevent the disease exists, though diet and moderate exercise may help. One experimental study found that patients often show high gluten sensitivity related to inflammation. Moderate exercise mainly reduces the effect of lung inflammation. After a 12-week exercise program, fatigue, depression and aerobic capacity all improved compared with controls. A small study also suggested that vagus nerve stimulation might reduce fatigue.

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• 7. Lymphoma and Outlook

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  About 5% of Sjögren's patients develop some form of lymphoid malignancy. Compared with other autoimmune diseases, the incidence of non-Hodgkin lymphoma, a cancer of white blood cells, is notably high. Patients with severe disease are much more likely to develop lymphoma than those with mild or moderate cases. The most common types are salivary extranodal marginal zone B cell lymphomas, known as MALT lymphomas, and diffuse large B-cell lymphoma.

  Researchers describe lymphoma development as a multistep process. It begins with chronic stimulation of autoimmune B cells, especially those that make rheumatoid factor, at the sites the disease targets. That stimulation raises the frequency of cancer-causing mutations. Apart from this higher lymphoma risk, patients show only modest or clinically insignificant decline in organ-related function.

  The burden of illness is still high. Sjögren's markedly reduces quality of life, and increased rates of disability affect the ability to work. The reduction is similar to that seen in rheumatoid arthritis, lupus and fibromyalgia.

  Studies of survival have been limited by small sample sizes and by the link between secondary Sjögren's and other autoimmune diseases. A 2010 study found a slight increase in mortality compared with the rest of the population. A 2016 study found that primary Sjögren's was not associated with higher all-cause mortality. It did suggest that patients with extraglandular involvement, vasculitis, hypocomplementaemia and cryoglobulinaemia may face increased risk.

  A 2021 meta-analysis reported a 46% increase in mortality. The risk was significantly greater in patients with older age, male gender, vasculitis, interstitial lung disease, low complements, positive anti-La/SSB and cryoglobulinaemia. Among people without other autoimmune disorders, life expectancy is unchanged.

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• 8. Names and New Drugs

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  In 1892, Jan Mikulicz-Radecki (1850-1905) described a 42-year-old man with enlarged parotid and lacrimal glands, a round-cell infiltrate and acinar atrophy. He is generally credited with the first description of the disease. The criteria he set out often led to misdiagnosis, because tuberculosis, infections, sarcoidosis and lymphoma can look similar. The term Mikulicz's syndrome is still occasionally used for lymphocytic infiltrates seen on salivary gland biopsies.

  In 1930, Henrik Sjögren (1899-1986), an ophthalmologist in Jönköping, Sweden, observed a patient with low secretions from the lacrimal and salivary glands. He coined the term keratoconjunctivitis sicca for dry eyes. In 1933 he published a doctoral thesis describing 19 females, most of them postmenopausal and with arthritis. He also clarified that dry eyes from water deficiency had no relation to xerophthalmia, which comes from vitamin A deficiency. The Board of Examiners criticized some clinical aspects, and the thesis was not well received.

  In 1951, Sjögren published an essential paper on 80 patients with keratoconjunctivitis sicca, 50 of whom also had arthritis. Follow-up conference trips about that paper sparked international interest, and the condition began to appear in the literature as Sjögren's syndrome.

  Research has since broadened. The United Kingdom Primary Sjögren's Syndrome Registry, a tissue biobank supported by the Medical Research Council, was established in 2010. Deficiencies of vitamin A and vitamin D have been associated with the disease. Saliva is a potential diagnostic tool because its makeup changes after onset, and lab-on-a-chip technology could make testing more convenient. In 2014, the Sjögren's Foundation announced a five-year goal to halve the average time to diagnosis.

  Drug research has moved too. In 2007, the most promising monoclonal antibodies under investigation were the anti-CD20 drug rituximab and the anti-CD22 drug epratuzumab, while anti-TNF-alpha and interferon alpha therapies seemed less effective. As of 2026, several investigational therapies were in late-stage development. In January 2026 the FDA granted ianalumab Breakthrough Therapy designation for Sjögren's disease, and telitacicept and dazodalibep are in phase III.

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