World Sjogren’s Disease Day (July 23)
Eminent Author, Medical Biochemist and Scientist, Technical Education consultant.
AGD Biomedicals (Pvt) LTD. Andheri East, Mumbai.
Sjögren’s disease (SD) affects a significant number of persons and estimated to impact between 0.5% to 1.0% of the general population(1). SD is a long-term autoimmune disease that primarily affects the exocrine glands of the body, particularly the lacrimal and salivary glands(2). The common organs affected by SD include eyes, mouth, and other organ systems, such as the nervous system, lungs, and kidneys(3). The following main symptoms have a moderate or major impact on life of patients that suffer from SD disease: Fatigue; joint pain; dry eyes; dry mouth; dry skin, dry nostrils, vaginal dryness, brain fog, blurred vision, constant eye discomfort, recurrent mouth infections, swollen parotid glands, dysphonia ( hoarseness), and difficulty in swallowing and eating(5,6). These symptoms can seriously impair quality of life of SD patients. Although SD is one of the most common autoimmune diseases, there is no one specific IVD laboratory diagnostic test to diagnose this and there is no specific remedy to treat and cure SD. However, combination of latest fifth generation IVD clinical laboratory tests are extremely useful to diagnose SD and rule out other autoimmune conditions and could be of help to assess overall health and guide supportive treatment decisions(7, 11).
Note
(A) World Sjogren’s disease SD) day is observed annually on July 23rd to coincide with the birthdate of Dr. Henrik Sjogren the Swedish ophthalmologist, who discovered SD in 1933.
(B) SD can affect kidneys causing tubulointerstitial nephritis (inflammation of the kidney tubules) or as immune complex-mediated glomerulonephritis, leading to the following various clinical conditions: Renal tubular acidosis, electrolyte imbalance, formation of kidney stones, etc(1,2).
(C) SD may cause interstitial lung disease and airway abnormalities in the lungs (1,2).
(D) SD can cause neurological complications in some patients leading to peripheral neuropathy, cognitive dysfunction, and may affect central nervous system leading to myelitis, optic neuropathy, etc(1,2).
(E ) SD can affect persons at any age, however, symptoms usually appear between 45-55 years of age. The SD symptoms may be mild affecting only eyes or mouth of moderate to severe affecting major organs of the body. Large number of SD patients (secondary SD) also have rheumatoid arthritis (RA) or a connective tissue disease, such as lupus(1,2). Autoimmune thyroiditis, multiple sclerosis and spondyloarthropathy are also observed in secondary SD.
Q1. What are the connective tissue diseases?
ANS: Connective tissue diseases are a group of disorders that affect the connective tissues in the body. Connective tissue provides structure and support to tissues and organs. Connective tissue diseases can be autoimmune or genetic and often lead to inflammation and damage to the connective tissues. Some common examples of connective tissue diseases are lupus, scleroderma, RA and Ehlers-Danlos syndrome(3).
Q2. What is the main cause of SD?
ANS: The exact cause of Sjögren’s disease is presently unknown. However, it may be due to combination of following one or more combinations: Genetic, autoimmune, environmental, viral, hormonal and other autoimmune disorders(3). Presently more than 20 responsible autoantibodies have been detected(1,2).
Q3. What are primary and secondary SD?
ANS: Primary SD is caused due to autoimmune antibodies produced against secretory glands of the body, while in secondary SD antibodies produced in other autoimmune conditions such as RA, connective tissue disorders, autoimmune hormonal disorders (e.g. thyroiditis), etc., also may attack secretory glands of the body.
Q4. What are the IVD clinical laboratory tests prescribed in suspected SD?
ANS (7,11) : Complete body profile clinical laboratory tests that mainly include: (1)Antinuclear antibody (ANA) test (2) Complete hemogram, (2) ESR, (3) C-reactive protein (4) Routine urine examination (5) Liver function tests (6) Kidney function tests (7) Lung function tests (8) Thyroid function tests (9) RA test (10) Serum electrolytes (11) Vitamins D and (12) Vitamin B12.
Q5. What are the impacts of fifth generation IVD clinical laboratory tests prescribed in suspected SD?
ANS : The following fifth generation blood tests can detect the antibodies associated with Sjogren’s disease that include: Anti-Ro (SS-A) and anti-La (SS-B) antibodies, rheumatoid factor, and antinuclear antibodies. However anti-SSA and anti-SSB tests are frequently not positive in SS(11).
Note :
Clinical laboratory tests play very important role in diagnosis and management of SD. Although any specific IVD blood test is unable to confirms the diagnosis of SD, these tests along with histopathology and imaging tests, could be useful to identify the characteristic features of the disease and rule out other clinical conditions. All these various tests are useful to detect autoantibodies, assess the glandular functions, and help to monitor disease progression(7).
Q6. What are the other various diagnostic tests, apart from clinical laboratory tests suggested to diagnose SD?
ANS (7,8) :
(A) Rose bengal test: A nontoxic stain (Rose bengal: RB) is used, that measures the state and function of the lacrimal glands. Few drops of RB are placed on the eyes. The distinctive colour of RB is useful in determining the state and functioning of the tear film and the rate of tear evaporation. Any significant colour change can indicate SS.
(B) Schirmer test: A strip of filter paper is placed inside the lower eyelid for five minutes. Wetness of filter paper is then measured with a ruler. Production of less than 5 mm of liquid is usually indication of SD. .
(C) Saliva flow tests: The patient is made to spits into a test tube after every one minute for 15 minutes. A resultant collection of less than 1.5 ml is considered a positive result for SD.
(D) Lip biopsy: In this test a sample of tissue from the inner lip/salivary gland is removed and examined it under a microscope. Lymphocytes clustered around salivary glands, and damage to these glands from inflammation can be studied using a microscope. Salivary gland ultrasonography is not invasive and may be useful in avoiding unnecessary biopsies in anti-SSA-negative patients.
(E) A radiological procedure is available as a reliable and accurate test for Sjögren’s disease, in the form of a sialogram. A contrast dye is injected into the salivary ducts and then radiological images are taken to see if blockages are present in the ducts.
Q7. What are the preventive measures to prevent occurrence of SD?
ANS : No prevention mechanism exists for Sjögren’s disease (SD) because of its complexity as an autoimmune disorder. However, lifestyle changes can reduce the risk factors related to development of SD or by reducing the severity of the condition for patients who have already been diagnosed.
Note :
Diet is strongly associated with the inflammation seen in many autoimmune-related diseases, including SS. An experimental study concluded that SD patients often show high sensitivity to gluten that directly relates to inflammation(9).
CASE STUDY
A 46-year-old female presented with dry eyes; dry mouth; dry nostrils, fatigue, brain fog, blurred vision, recurrent mouth infections, and hoarseness. She was advised the following clinical laboratory tests:
Antinuclear antibody test (ANA): Positive (Normal: Negative)
Interpretation :
ANA test is positive in SD and also in connective tissue autoimmune disorders.
However, from the symptoms and history of the patient, it appears that she was suffering from Sjogren’s disease (Refer to answers of questions: 1-6).
COMPLETE HEMOGRAM
| TEST | RESULT | REFERENCE RANGE |
| Hemoglobin | 10.5 g/dl | 12.5–15.5 g/dl |
| Total erythrocyte count | 3.6 X 1012/l | 4.5.0 ± 0.5 X 1012 /l |
| Total leukocyte count | 6.7 X 109/l | 7.0 ± 3.0 X 109/l |
| Differential leukocyte count | ||
| Neutrophils | 62% | 40–75% |
| Lymphocytes | 36% | 20–45 % |
| Eosinophils | 2% | 1–4 % |
| Stained peripheral blood smear | ||
| Microscopic observations | Microcytes + | Normal cells |
| PCV | 31% | 36–48% |
| MCV | 80 fL | 82–92 fL |
| MCH | 24 pg | 27–32 pg |
| MCHC | 34 % | 32–36 % |
| RDW- CV | 12.8 | 12–14 |
| Platelet count | 185 X 109/l | 150–400 X 109/l |
Interpretation:
Low values of blood hemoglobin, MCV, MCH, and normal MCHC indicate Normochromic microcytic anemia (Anemia of chronic infections).
Note:
(A) Complete hemogram (CBC) can diagnose anemia with specific type and also leukopenia (low white blood cell count), and thrombocytopenia (low platelet count), which may be associated with SD or related drugs used in the treatment regime.
Erythrocyte sedimentation rate: 78 mm/after 1 hr (Normal: 0-20 mm/after 1 hr).
High sensitivity C-reactive protein: 18 mg/ l (< 1 mg/l)
Interpretation:
High values of ESR and C-reactive protein indicate significant increase in the inflammatory status in the body of the patient.
Other body profile tests:
Diabetic profile test, Kidney profile tests, Liver profile tests, Lung profile tests, Thyroid profile tests, Serum electrolytes and vitamins (D and B12), RA test: No significant findings, except mild increases in SGPT and SGOT and mild decrease in Vitamin D.
Routine urine examination: No significant findings
Routine feces examination: No significant findings
Interpretation: In this case it seems, secretary glands of the patient’s eyes and mouth are affected (and not other glands such as liver, kidneys, lungs and thyroid gland.
Note :
(A) Presently, there is no cure or a specific treatment on Sjögren’s disease to permanently restore specific gland secretions. Instead, treatment is generally symptomatic and supportive(10).
(B) In autoimmune diseases, the immunosuppressive treatments based on steroids and anti-mitotic agents used so far are now in the process of replacement with more immune selective drugs. These new therapies are in the form of antagonist and cytotoxic antibodies.
Supportive treatment modes(10):
(A) Eye care: Cyclosporin eye drops prescribed by the ophthalmologist could be useful to decrease the symptoms of dry eyes. Use of goggles is useful to increase local humidity also retain tears on the ocular surface for a longer time.
(B) Salivary flow stimulants: Drugs such as cevimeline and pilocarpine as prescribed by the ophthalmologists could be effective to stimulate and increase salivary flow. Pilocarpine drug facilitates formation of tears, as well as saliva in the mouth and increase in intestinal secretions.
(C ) Vaginal dryness: Personal lubricants are recommended to decrease irritation or pain that may cause from dryness in the vaginal and vulval areas.
(D) Musculoskeletal symptoms: Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed to treat musculoskeletal symptoms. For patients with severe complications, corticosteroids or immunosuppressive drugs (such as methotrexate) may be prescribed. However, these drugs are also responsible for side effects such as nausea, headache, loss of appetite, dizziness, hair loss, liver toxicity, stomach cramps, and increased risk of infections.
(E) Preventive dental treatment: The lack of saliva associated with xerostomia leads to the proliferation of bacteria in mouth that cause tooth cavities. Specific toothpastes prescribed by the dentists are necessary to prevent tooth decay.
References
(1) Baer AN, Hammitt KM (July 2021). “Sjögren’s Disease, Not Syndrome”. Arthritis & Rheumatology. 73 (7): 1347–1348. doi:10.1002/art.41676. ISSN 2326-5191. PMID 33559389.
(2) Voulgarelis M., Tzioufas A. G. (2010). “Pathogenetic mechanisms in the initiation and perpetuation of Sjögren’s syndrome”. Nature Reviews. Rheumatology. 6 (9): 529–537. doi:10.1038/nrrheum.2010.118. PMID 20683439. S2CID 8755126.
(3) Singh AG, Singh S, Matteson EL (March 2016). “Rate, risk factors and causes of mortality in patients with Sjögren’s syndrome: a systematic review and meta-analysis of cohort studies”. Rheumatology. 55 (3): 450–60. doi:10.1093/rheumatology/kev354. PMC 5009445. PMID 26412810.
(4) Saldanha IJ, Bunya VY, McCoy SS, Makara M, Baer AN, Akpek EK (2020). “Ocular Manifestations and Burden Related to Sjögren Syndrome: Results of a Patient Survey”. American Journal of Ophthalmology. 219: 40–48. doi:10.1016/j.ajo.2020.05.043. PMC 7606749. PMID 32569739.
(5) McCoy SS, Woodham M, Bartels CM, Saldanha IJ, Bunya VY, Maerz N, Akpek EK, Makara MA, Baer AN (2022). “Symptom-Based Cluster Analysis Categorizes Sjögren’s Disease Subtypes: An International Cohort Study Highlighting Disease Severity and Treatment Discordance”. Arthritis & Rheumatology. 74 (9): 1569–1579. doi:10.1002/art.42238. PMC 9427679. PMID 35594474.
(6) McCoy SS, Woodham M, Bunya VY, Saldanha IJ, Akpek EK, Makara MA, Baer AN (2022). “A comprehensive overview of living with Sjögren’s: Results of a National Sjögren’s Foundation survey”. Clinical Rheumatology. 41 (7): 2071–2078. doi:10.1007/s10067-022-06119-w. PMC 9610846. PMID 35257256
(7) “Sjögren Syndrome (SS) Laboratory Testing | Beutner Labs”. Beutner Laboratories. Retrieved 2025-05-30.
(8) Schoppmeier CM, Helpap J, Hagemeier A, Wicht MJ, Barbe AG (August 2022). “Using the modified Schirmer test for dry mouth assessment: A cross-sectional study”. European Journal of Oral Sciences. 130 (4): e12880. doi:10.1111/eos.12880. PMID 35692181. S2CID 249622808
(9)Lidén M, Kristjánsson G, Valtýsdóttir S, Hällgren R (August 2007). “Gluten sensitivity in patients with primary Sjögren’s syndrome”. Scand. J. Gastroenterol. 42 (8): 962–7. doi:10.1080/00365520701195345. PMID 17613926. S2CID 26333122
(10) Vivino FB (2009). “The treatment of Sjögren’s syndrome patients with Pilocarpine-tablets”. Scandinavian Journal of Rheumatology. 30 (115): 1–13. doi:10.1080/030097401300
(11) Godkar PB, Godkar DP. Text book of Medical laboratory technology (4th edition, 2024), Bhlani Publishers, Mumbai. India.
