Sjögren's disease

Did You Know?

• Around 20 autoantibodies could be involved in Sjögren's disease.
• Studies on polymorphisms of HLA-DR and HLA-DQ gene regions show differential susceptibility to the disease.
• An experimental study concluded that Sjögren's disease patients often show high gluten sensitivity that directly relates to inflammation.

Signs and symptoms

Sjögren's disease is primarily marked by persistent dryness in the mouth and eyes, known as keratoconjunctivitis sicca. Dryness can also affect the skin, nose, and vagina. Beyond dryness, many people experience fatigue, joint and muscle pain, trouble sleeping, brain fog, a chronic cough, numbness in the limbs, and thyroid issues. A 2021 survey found that fatigue, dry eyes, dry mouth, joint pain, trouble sleeping, eye discomfort, muscle pain, and brain fog were the symptoms most often reported as having a major or moderate impact on daily life. The disease can involve other organs, including the kidneys, lungs, liver, pancreas, blood vessels, and brain. Kidney problems may include autoimmune tubulointerstitial nephritis, which can lead to protein in the urine or renal tubular acidosis. Women with specific antibodies (anti-Ro/SS-A and anti-La/SS-B) face a higher risk of having a baby with neonatal lupus and congenital heart block, which may require a pacemaker. Type I cryoglobulinemia is another known complication. Symptoms often start gradually and can be mistaken for medication side effects, aging, or a dry environment. The course of the disease varies: some people have only mild dryness, while others experience severe issues like blurred vision, recurrent mouth infections, swollen parotid glands, hoarseness, and trouble swallowing. Debilitating fatigue and joint pain can significantly lower quality of life.

Pathogenesis

The pathogenetic mechanisms of Sjögren's disease have not been fully elucidated. It was originally proposed as a self-perpetuating, immune system-mediated loss of exocrine glands, specifically acinar and ductal cells, which explains the lack of saliva and lacrimal fluid but not the systemic effects. In the presence of a susceptible genetic background, environmental and hormonal factors are thought to trigger infiltration of lymphocytes, including CD4+ T cells, B cells, and plasma cells, causing glandular dysfunction in the salivary and lacrimal glands. The disease is associated with increased levels of IL-1RA in cerebrospinal fluid, suggesting increased activity in the interleukin 1 system followed by autoregulatory upregulation of IL-1RA. Interleukin 1 likely is the marker for fatigue, while decreased IL-1RA in saliva may be responsible for mouth inflammation and dryness. Patients with secondary Sjögren's disease often exhibit signs and symptoms of their primary rheumatic disorders, such as systemic lupus erythematosus, rheumatoid arthritis, or systemic sclerosis.

Diagnosis

Diagnosing Sjögren's disease is complicated by the range of symptoms and their similarity to other conditions, as well as the fact that patients may approach different specialties for treatment. Dry eyes and dry mouth are common symptoms, especially in people over 40, and may be attributed to medications, a dry environment, or aging. No specific and non-invasive diagnostic test exists. A combination of several tests can eventually diagnose the disease. Blood tests can detect high levels of antibodies such as antinuclear antibody (ANA) and rheumatoid factor; typical Sjögren's ANA patterns are SSA/Ro and SSB/La, with anti-SSB/La being far more specific. However, anti-SSA and anti-SSB tests are frequently not positive. The rose bengal test uses a nontoxic dye to measure the state and function of the lacrimal glands. Schirmer's test measures tear production by holding a strip of filter paper inside the lower eyelid for five minutes; producing less than 5 mm of liquid is usually indicative of Sjögren's. A slit-lamp examination can reveal dryness on the surface of the eye. Schirmer strips can also be used to test oral dryness. The most specific extant diagnostic test requires a lip biopsy.

Treatment

Neither a cure nor a specific treatment is known to restore gland secretion; treatment is generally symptomatic and supportive. For dry eyes, artificial tears, medications to reduce inflammation, punctal plugs, or other surgery to shut the tear ducts may be tried. Prescription eyedrops such as cyclosporine, lifitegrast, and perfluorohexyloctane can suppress inflammation or prevent tear evaporation. For dry mouth, chewing sugar-free gum, sipping water, or using a saliva substitute may help. Prescription drugs like cevimeline and pilocarpine can stimulate salivary flow. For joint or muscle pain, ibuprofen or other nonsteroidal anti-inflammatory drugs (NSAIDs) may be used. Medications that can cause dryness, such as antihistamines, may be stopped. Vaginal dryness, vulvodynia, and dyspareunia are often reported; personal lubricants are recommended. For severe complications, corticosteroids, immunosuppressive drugs, or intravenous immunoglobulins may be prescribed. Disease-modifying antirheumatic drugs such as methotrexate or hydroxychloroquine may be helpful, though these drugs have side effects including nausea, loss of appetite, dizziness, hair loss, stomach aches, headache, liver toxicity, and increased risk of infections.