Sjögren's disease

In a 2021 article on Sjogren's patients, a majority of individuals stated that eight Sjogren's symptoms had a major or moderate impact on their life: fatigue (79%); dry eyes (75%); dry mouth (73%); joint pain (65%); trouble sleeping (64%); eye discomfort (60%); muscle pain (56%); and brain fog (54%).{{cite journal | doi=10.1016/j.ajo.2020.05.043 | title=Ocular Manifestations and Burden Related to Sjögren Syndrome: Results of a Patient Survey | date=2020 | last1=Saldanha | first1=Ian J. | last2=Bunya | first2=Vatinee Y. | last3=McCoy | first3=Sara S. | last4=Makara | first4=Matthew | last5=Baer | first5=Alan N. | last6=Akpek | first6=Esen K. | journal=American Journal of Ophthalmology | volume=219 | pages=40–48 | pmid=32569739 | pmc=7606749 }}{{cite journal | pmc=9427679 | date=2022 | last1=McCoy | first1=S. S. | last2=Woodham | first2=M. | last3=Bartels | first3=C. M. | last4=Saldanha | first4=I. J. | last5=Bunya | first5=V. Y. | last6=Maerz | first6=N. | last7=Akpek | first7=E. K. | last8=Makara | first8=M. A. | last9=Baer | first9=A. N. | title=Symptom-Based Cluster Analysis Categorizes Sjögren's Disease Subtypes: An International Cohort Study Highlighting Disease Severity and Treatment Discordance | journal=Arthritis & Rheumatology | volume=74 | issue=9 | pages=1569–1579 | doi=10.1002/art.42238 | pmid=35594474 }}{{cite journal | pmc=9610846 | date=2022 | last1=McCoy | first1=S. S. | last2=Woodham | first2=M. | last3=Bunya | first3=V. Y. | last4=Saldanha | first4=I. J. | last5=Akpek | first5=E. K. | last6=Makara | first6=M. A. | last7=Baer | first7=A. N. | title=A comprehensive overview of living with Sjögren's: Results of a National Sjögren's Foundation survey | journal=Clinical Rheumatology | volume=41 | issue=7 | pages=2071–2078 | doi=10.1007/s10067-022-06119-w | pmid=35257256 }}

Primary symptoms are dryness (dry mouth and dry eyes), pain and fatigue.{{cite journal |last1=Cornec |first1=Divi |last2=Devauchelle-Pensec |first2=Valérie |last3=Mariette |first3=Xavier |last4=Jousse-Joulin |first4=Sandrine |last5=Berthelot |first5=Jean-Marie |last6=Perdriger |first6=Aleth |last7=Puéchal |first7=Xavier |last8=Le Guern |first8=Véronique |last9=Sibilia |first9=Jean |last10=Gottenberg |first10=Jacques-Eric |last11=Chiche |first11=Laurent |last12=Hachulla |first12=Eric |last13=Yves Hatron |first13=Pierre |last14=Goeb |first14=Vincent |last15=Hayem |first15=Gilles |last16=Morel |first16=Jacques |last17=Zarnitsky |first17=Charles |last18=Dubost |first18=Jean Jacques |last19=Saliou |first19=Philippe |last20=Pers |first20=Jacques Olivier |last21=Seror |first21=Raphaèle |last22=Saraux |first22=Alain |title=Severe Health-Related Quality of Life Impairment in Active Primary Sjögren's Syndrome and Patient-Reported Outcomes: Data From a Large Therapeutic Trial |journal=Arthritis Care & Research |date=April 2017 |volume=69 |issue=4 |pages=528–535 |doi=10.1002/acr.22974 |pmid=27390310 |s2cid=22904103 |doi-access=free }} Other symptoms can include dry skin, vaginal dryness, a chronic cough, numbness in the arms and legs, feeling tired, muscle and joint pains, and thyroid problems. Those affected are also at an increased risk (15%) of lymphoma.{{cite journal |last1=Brito-Zerón |first1=Pilar |last2=Baldini |first2=Chiara |last3=Bootsma |first3=Hendrika |last4=Bowman |first4=Simon J. |last5=Jonsson |first5=Roland |last6=Mariette |first6=Xavier |last7=Sivils |first7=Kathy |last8=Theander |first8=Elke |last9=Tzioufas |first9=Athanasios |last10=Ramos-Casals |first10=Manuel |title=Sjögren syndrome |journal=Nature Reviews Disease Primers |date=7 July 2016 |volume=2 |issue=1 |pages=16047 |doi=10.1038/nrdp.2016.47 |pmid=27383445 |s2cid=4049076 |hdl=11568/809074 |hdl-access=free }}{{cite book| url= https://books.google.com/books?id=3zM9yCy8uqUC&pg=PA389 |title= Primer on the rheumatic diseases|last1=John H.| first1= Klippel| date =2008 |publisher= Springer |isbn= 978-0-387-68566-3 |edition= 13th |location= New York, New York |page=389|access-date=15 July 2016| archive-url= https://web.archive.org/web/20160815233354/https://books.google.ca/books?id=3zM9yCy8uqUC&pg=PA389 |archive-date=15 August 2016| url-status= live}}

File:Sjogrens Syndrome.jpg

The hallmark symptom of Sjögren's disease is dry mouth and keratoconjunctivitis sicca (dry eyes). Vaginal dryness, dry skin, and dry nose may also occur. Other organs of the body may also be affected,{{cite journal|last1=Sandhya|first1=Pulukool|last2=Jeyaseelan|first2=Lakshmanan|last3=Scofield|first3=Robert Hal|last4=Danda|first4=Debashish|date=26 June 2015|title=Clinical Characteristics and Outcome of Primary Sjogren's Syndrome: A Large Asian Indian Cohort|journal=The Open Rheumatology Journal|language=en|volume=9|issue=1|pages=36–45|doi=10.2174/1874312901409010036|pmid=26161156|pmc=4493630|doi-access=free}} including the kidneys, blood vessels, lungs, liver, pancreas, and brain.{{cite web|title=Sjögren's Syndrome Information Page|url=https://www.ninds.nih.gov/Disorders/All-Disorders/Sj%C3%B6grens-Syndrome-Information-Page#disorders-r1|website=nih.gov|access-date=18 May 2018|archive-date=19 May 2018|archive-url=https://web.archive.org/web/20180519032953/https://www.ninds.nih.gov/Disorders/All-Disorders/Sj%C3%B6grens-Syndrome-Information-Page#disorders-r1|url-status=dead}}{{cite web|title=Indian Rheumatology Association {{!}} IRA E-NEWSLETTER|url=https://www.indianrheumatology.org/ira-e-newsletter/issue/2020/july/patients-portal/sjogren-syndrome-expert-speaks|archive-url=https://web.archive.org/web/20200706070816/https://www.indianrheumatology.org/ira-e-newsletter/issue/2020/july/patients-portal/sjogren-syndrome-expert-speaks|url-status=dead|archive-date=July 6, 2020|access-date=6 July 2020|website=www.indianrheumatology.org}}

In some people with Sjögren's disease, skin dryness may be the result of lymphocytic infiltration into skin glands. The symptoms may develop insidiously, with the diagnosis often not considered for several years because sicca (dryness) may be attributed to medications, a dry environment, or aging, or may be regarded as not of a severity warranting the level of investigation necessary to establish the presence of the underlying autoimmune disorder.

Sjögren's disease can damage vital organs, with symptoms that may plateau or worsen, or go into remission, as with other autoimmune diseases. Some people may experience only the mild symptoms of dry eyes and mouth, while others have symptoms of severe disease. Many patients can treat problems symptomatically. Others experience blurred vision, constant eye discomfort, recurrent mouth infections, swollen parotid glands, dysphonia (vocal disorders including hoarseness), and difficulty in swallowing and eating. Debilitating fatigue and joint pain can seriously impair quality of life. Some patients can develop kidney involvement (autoimmune tubulointerstitial nephritis) leading to proteinuria (excess protein in urine), urinary concentrating defect, and distal renal tubular acidosis.{{cite web|title=Indian Rheumatology Association {{!}} IRA E-NEWSLETTER|url=https://www.indianrheumatology.org/ira-e-newsletter/issue/2020/july/rheumatologists-and-health-professionals/electrolyte-abnormalities-in-sjgren-syndrome|access-date=6 July 2020|website=www.indianrheumatology.org|archive-date=6 July 2020|archive-url=https://web.archive.org/web/20200706070815/https://www.indianrheumatology.org/ira-e-newsletter/issue/2020/july/rheumatologists-and-health-professionals/electrolyte-abnormalities-in-sjgren-syndrome|url-status=dead}}

Among the complications discussed above, women with anti-Ro/SS-A and anti-La/SS-B antibodies who become pregnant have an increased rate of neonatal lupus erythematosus with congenital heart block requiring a pacemaker.{{cite journal |title=Late neonatal lupus erythematosus onset in a child born of a mother with primary Sjögren's syndrome |journal= Ann. Rheum. Dis. |volume=63 |issue=11 |pages=1496–7 |date=November 2004 |pmid=15479901 |pmc=1754813 |doi=10.1136/ard.2003.014944 |last1=Manthorpe |first1=R |last2=Svensson |first2=A |last3=Wirestrand |first3=LE}} Type I cryoglobulinemia is a known complication of Sjögren's disease.{{cite journal|title=Cryoglobulinemia in primary Sjögren's syndrome: prevalence and clinical characteristics in a series of 115 patients |journal=Semin Arthritis Rheum. |volume=28 |issue=3 |pages= 200–5 |date= December 1998 |pmid=9872481 |doi=10.1016/S0049-0172(98)80037-1|last1=Ramos-Casals| first1= Manel| last2= Cervera |first2= Ricard|last3=Yagüe|first3=Jordi|last4=García-Carrasco |first4= Mario| last5= Trejo| first5= Olga| last6= Jiménez| first6= Sonia|last7=Morlà|first7=Rosa M|last8=Font|first8=Josep|last9=Ingelmo|first9=Miguel}}

Sjögren's disease can affect such organs as the liver, pancreas, kidneys, lungs, and central nervous system.{{cite web |title=Symptoms |url=https://www.sjogrens.org/understanding-sjogrens/symptoms |website=Sjögren's Foundation |access-date=14 April 2020}}

Sjögren's disease is associated with a number of other medical conditions, many of which are autoimmune or rheumatic disorders, such as celiac disease,{{cite journal| vauthors= Lundin KE, Wijmenga C|title=Coeliac disease and autoimmune disease–genetic overlap and screening|journal=Nat Rev Gastroenterol Hepatol|volume=12|issue=9|pages=507–15|date=Sep 2015|pmid=26303674|doi=10.1038/nrgastro.2015.136|s2cid=24533103|type=Review}}{{cite journal|vauthors=Denham JM, Hill ID|title=Celiac disease and autoimmunity: review and controversies|journal=Curr Allergy Asthma Rep|volume=13|issue=4|pages=347–53|date=August 2013 |pmid= 23681421| pmc= 3725235 |doi=10.1007/s11882-013-0352-1|type=Review}} fibromyalgia, systemic lupus erythematosus (lupus), autoimmune thyroiditis, multiple sclerosis and spondyloarthropathy,{{cite journal|vauthors=Gabriel SE, Michaud K|title=Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases| journal=Arthritis Res Ther|volume=11|issue=3|page=229|date=2009|pmid=19519924|pmc=2714099|doi=10.1186/ar2669|type=Review |doi-access=free }} and several malignancies, principally non-Hodgkin lymphoma.{{cite journal|vauthors=Papageorgiou A, Voulgarelis M, Tzioufas AG|title=Clinical picture, outcome and predictive factors of lymphoma in Sjӧgren syndrome|journal=Autoimmun Rev|volume=14|issue=7|pages=641–9|date=Jul 2015|pmid=25808075|doi=10.1016/j.autrev.2015.03.004|type=Review}}

Sjogren's is the second most common cause of dysautonomia.{{cite journal | doi=10.3389/fimmu.2021.702505 | doi-access=free | title=Autonomic Nervous System Dysfunction in Primary Sjögren's Syndrome | date=2021 | last1=Davies | first1=Kristen | last2=Ng | first2=Wan-Fai | journal=Frontiers in Immunology | volume=12 | pmid=34381453 | pmc=8350514 }}{{cite journal | pmid=25622919 | date=2015 | last1=Imrich | first1=R. | last2=Alevizos | first2=I. | last3=Bebris | first3=L. | last4=Goldstein | first4=D. S. | last5=Holmes | first5=C. S. | last6=Illei | first6=G. G. | last7=Nikolov | first7=N. P. | title=Predominant Glandular Cholinergic Dysautonomia in Patients with Primary Sjögren's Syndrome | journal=Arthritis & Rheumatology | volume=67 | issue=5 | pages=1345–1352 | doi=10.1002/art.39044 | pmc=4414824 }}{{cite web | url=https://my.clevelandclinic.org/health/diseases/6004-dysautonomia | title=Dysautonomia: Malfunctions in Your Body's Automatic Functions }}{{cite web | url=https://sjogrens.org/blog/2023/dysautonomia-in-sjogrens | title=Dysautonomia in Sjögren's | date=26 October 2023 }}

While the exact cause is unclear, it is believed to involve a combination of genetics and an environmental trigger such as exposure to a virus or bacterium. It can occur independently of other health problems or as a result of another connective tissue disorder.{{cite book|url=https://books.google.com/books?id=Axo9DAAAQBAJ&pg=PA10|title=Sjögren's Syndrome |last1= Ng| first1= Wan-Fai |date=2016|publisher=Oxford University Press|isbn=978-0-19-873695-0|pages=10–11| archive-url= https://web.archive.org/web/20160815195550/https://books.google.ca/books?id=Axo9DAAAQBAJ&pg=PA10|archive-date=15 August 2016|url-status= live}} Sjögren's disease may be associated with other autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or systemic sclerosis. The inflammation that results progressively damages the glands. Diagnosis is by biopsy of moisture-producing glands and blood tests for specific antibodies. On biopsy there are typically lymphocytes within the glands.

The cause of Sjögren's disease is unknown, but it may be the influence of a combination of genetic, environmental, and other factors, as is the case with many other autoimmune disorders.{{cite journal | vauthors = Borchers AT, Naguwa SM, Keen CL, Gershwin ME | title = Immunopathogenesis of Sjögren's syndrome | journal = Clin Rev Allergy Immunol | volume = 25 | issue = 1 | pages = 89–104 | date = August 2003 | pmid = 12794264 | doi = 10.1385/CRIAI:25:1:89 | s2cid = 7098743 }} Around 20 autoantibodies could be involved.{{cite journal |last1=Martín-Nares |first1=Eduardo |last2=Hernández-Molina |first2=Gabriela |title=Novel autoantibodies in Sjögren's syndrome: A comprehensive review |journal=Autoimmunity Reviews |date=February 2019 |volume=18 |issue=2 |pages=192–198 |doi=10.1016/j.autrev.2018.09.003|pmid=30572138 |s2cid=58656692 }}

The observation of high rates of autoimmune disorders in families with a history of Sjögren's disease is linked with a genetic predisposition to the disease.{{cite journal | author = Voulgarelis M., Tzioufas A. G. | year = 2010 | title = Pathogenetic mechanisms in the initiation and perpetuation of Sjögren's syndrome | journal = Nature Reviews. Rheumatology | volume = 6 | issue = 9| pages = 529–537 | doi=10.1038/nrrheum.2010.118| pmid = 20683439 | s2cid = 8755126 }} Studies on the polymorphisms of human leukocyte antigen (HLA)-DR and HLA-DQ gene regions in Sjögren's patients show differential susceptibility to the disease as the result of different types of the resulting autoantibody production.

Since Sjögren's disease is associated with a high prevalence in women, sex hormones, especially estrogen, are believed to affect humoral and cell-mediated immune responses affecting susceptibility to the disease. Androgens are generally considered to prevent autoimmunity.{{cite journal | vauthors = Delaleu N, Jonsson R, Koller MM | title = Sjögren's syndrome | journal = Eur. J. Oral Sci. | volume = 113 | issue = 2 | pages = 101–13 | date = April 2005 | pmid = 15819815 | doi = 10.1111/j.1600-0722.2004.00183.x }} Studies on mice models suggest estrogen deficiency stimulates presentation of autoantigens, inducing Sjögren's-like symptoms.

Microchimerism of fetal cells (offspring lymphoid cells in maternal circulation) may generate autoimmunity in women who have previously been pregnant.{{cite journal | author = Whitacre C. C. | year = 2001 | title = Sex differences in autoimmune disease | journal = Nat. Immunol. | volume = 2 | issue = 9| pages = 777–780 | doi=10.1038/ni0901-777| pmid = 11526384 | s2cid = 6743550 }} Generation of an autoimmune potential via microchimerism may lead to a switch from a silent form of autoimmunity with age-dependent decrease in self-tolerance.

Viral proteins, engulfed molecules, or degraded self-structures may initiate autoimmunity by molecular mimicry and increase the chances of Sjögren's disease development. Epstein–Barr virus, hepatitis C, and human T-cell leukemia virus-1 are among the most studied infectious agents in Sjögren's disease. To date, no direct cause-and-effect relationship has been identified between these pathogens and the development of Sjögren's disease. Damaged self-structures targeted for apoptosis may be mistakenly exposed to the immune system, triggering autoimmunity in exocrine glands, which are often prone to autoimmune responses.

The pathogenetic mechanisms of Sjögren's disease have not been fully elucidated, resulting in the lack of pathophysiology knowledge of the management of this autoimmune exocrinopathy. Although the numerous factors contributing to the progression of this disease have made discovering the exact origin and cause difficult, major advances over the past decade have contributed to a proposed set of pathogenic events that occur before the diagnosis of Sjögren's disease.

Sjögren's disease was originally proposed as a specific, self-perpetuating, immune system-mediated loss of exocrine glands, specifically acinar and ductal cells. Although this explains the more obvious symptoms (such as the lack of saliva and lacrimal fluid), it does not explain the more widespread systemic effects seen in the progression of the disease.{{citation needed|date=December 2020}}

In the presence of a susceptible genetic background, both environmental and hormonal factors are thought capable of triggering the infiltration of lymphocytes, specifically CD4+ T cells, B cells, and plasma cells, causing glandular dysfunction in the salivary and lacrimal glands.Mohammad Dezfulian, Tomasz Kula, Thomas Pranzatelli, Nolan Kamitaki, Qingda Meng, Bhuwan Khatri, Paola Perez et al. "TScan-II: A genome-scale platform for the de novo identification of CD4+ T cell epitopes." Cell 186, no. 25 (2023): 5569-5586. DOI: [https://doi.org/10.1016/j.cell.2023.10.024 10.1016/j.cell.2023.10.024]

Sjögren's disease is associated with increased levels in cerebrospinal fluid (CSF) of IL-1RA, an interleukin 1 antagonist. This suggests that the disease begins with increased activity in the interleukin 1 system, followed by an autoregulatory upregulation of IL-1RA to reduce the successful binding of interleukin 1 to its receptors. Interleukin 1 likely is the marker for fatigue, but increased IL-1RA is observed in the CSF and is associated with increased fatigue through cytokine-induced sickness behavior.{{cite journal|doi=10.1016/j.bbi.2009.06.151|pmid=19560535|title=Fatigue in primary Sjögren's disease – A link to sickness behaviour in animals?|year=2009|last1=Harboe|first1=Erna|last2=Tjensvoll|first2=Anne Bolette|last3=Vefring|first3=Hege K.| last4= Gøransson |first4=Lasse G.|last5=Kvaløy|first5=Jan Terje|last6=Omdal|first6=Roald|journal=Brain, Behavior, and Immunity| volume= 23| issue=8|pages=1104–8|s2cid=43828817}} However, Sjögren's disease is characterized by decreased levels of IL-1ra in saliva, which could be responsible for mouth inflammation and dryness.{{cite journal |pmid= 9646842| year= 1998| last1= Perrier |first1= S| last2= Coussediere|first2=C|last3=Dubost|first3=JJ|last4=Albuisson|first4=E|last5=Sauvezie|first5=B|title=IL-1 receptor antagonist (IL-1RA) gene polymorphism in Sjögren's disease and rheumatoid arthritis|volume=87|issue=3|pages=309–13|journal=Clinical Immunology and Immunopathology|doi=10.1006/clin.1998.4520}} Patients with secondary Sjögren's disease also often exhibit signs and symptoms of their primary rheumatic disorders, such as systemic lupus erythematosus, rheumatoid arthritis, or systemic sclerosis.{{citation needed|date=October 2020}}

The genetic locus most significantly associated with primary SS is the major histocompatibility complex/human leukocyte antigen (MHC/HLA) region, as demonstrated by the preliminary results of the first genome-wide association study.{{cite journal |last1=Reveille |first1=JD |title=The molecular genetics of systemic lupus erythematosus and Sjögren's disease |journal=Current Opinion in Rheumatology |date=October 1992 |volume=4 |issue=5 |pages=644–56 |pmid=1419498}} This study included data from a discovery cohort of 395 patients of European ancestry with primary Sjögren's disease, and 1,975 healthy control individuals, and from a replication study that comprised 1,234 cases and 4,779 healthy controls. Associations with polymorphisms located at six independent loci were also detected; IRF5, STAT4, BLK, IL12A, TNIP1, and CXCR5. This also suggested the activation of the innate immune system, notably through the IFN system, B-cell activation through CXCR5-directed recruitment to lymphoid follicles and B-cell receptor (BCR) activation involving BLK, and T-cell activation owing to HLA susceptibility and the IL-12-IFN-γ-axis.{{cite journal |last1=Lessard |first1=C. J. |last2=Li |first2=H. |last3=Ice |first3=J. A. |last4=Adrianto |first4=I. |last5=Jonsson |first5=R. |last6=Illei |first6=G. G. |last7=Rischmueller |first7=M. |last8=Nordmark |first8=G. |last9=Mariette |first9=X. |last10=Miceli-Richard |first10=C. |last11=Wahren Herlenius |first11=M. |last12=Witte |first12=T. |last13=Brennan |first13=M. |last14=Omdal |first14=R. |last15=Gaffney |first15=P. M. |last16=Lessard |first16=J. A. |last17=Rönnblom |first17=L. |last18=Ng |first18=W.-F. |last19=Rhodus |first19=N. |last20=Segal |first20=B. |last21=Scofield |first21=R. H. |last22=James |first22=J. A. |last23=Anaya |first23=J.-M. |last24=Montgomery |first24=C. G. |last25=Harley |first25=J. B. |last26=Moser Sivils |first26=K. |title=OP0020 Identification of Multiple Sjögren's Syndrome Susceptibility Loci |journal=Annals of the Rheumatic Diseases |date=June 2013 |volume=72 |issue=Suppl 3 |pages=A54.3–A55 |doi=10.1136/annrheumdis-2013-eular.225 |s2cid=84998601 }}

Patients of different ethnic origins carry different HLA-susceptibility alleles, of which HLA-DR and HLA-DQ are involved in the pathogenesis of Sjögren's disease. For example, patients from Northern and Western Europe and North America show a high prevalence of B8, DRw52, and DR3 genes.{{cite journal | vauthors = Kang HI, Fei HM, Saito I, Sawada S, Chen SL, Yi D, Chan E, Peebles C, Bugawan TL, Erlich HA | title = Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjögren's syndrome | journal = J. Immunol. | volume = 150 | issue = 8 Pt 1 | pages = 3615–23 | date = April 1993 | doi = 10.4049/jimmunol.150.8.3615 | pmid = 8468491 | s2cid = 1453558 | doi-access = free }} HLA class II alleles are associated with the presence of specific subsets of autoantibodies, rather than with the disease itself.{{cite journal | vauthors = Bolstad AI, Wassmuth R, Haga HJ, Jonsson R | title = HLA markers and clinical characteristics in Caucasians with primary Sjögren's syndrome | journal = J. Rheumatol. | volume = 28 | issue = 7 | pages = 1554–62 | date = July 2001 | pmid = 11469461 }} Autoantibodies refer to the loss of B-cell tolerance leading to the production of antibodies directed against diverse organ-specific and organ nonspecific antigens. Association between HLA and SS is restricted to patients with anti-SSA/Ro or anti-SSB/La antibodies. Seropositivity for anti-Ro and anti-La is associated with greater severity and longer duration of disease, and findings of their high abundance from the salivary glands of Sjögren's patients suggests their imperative role in the pathogenesis of SS.{{cite journal | vauthors = Fei HM, Kang H, Scharf S, Erlich H, Peebles C, Fox R | title = Specific HLA-DQA and HLA-DRB1 alleles confer susceptibility to Sjögren's disease and autoantibody production | journal = J. Clin. Lab. Anal. | volume = 5 | issue = 6 | pages = 382–91 | date = 1991 | pmid = 1685512 | doi = 10.1002/jcla.1860050604 | s2cid = 39754064 }}

Beyond genetics, epigenetic abnormality related to DNA methylation, histone acetylation, or microRNA expression probably has a key role in the pathogenesis of autoimmune diseases, including Sjögren's disease, though research in this area is very limited.{{cite journal | author = Lu Q | year = 2013 | title = The critical importance of epigenetics in autoimmunity | journal = J. Autoimmun. | volume = 41 | pages = 1–5 | doi=10.1016/j.jaut.2013.01.010| pmid = 23375849 | url = https://tede.ufrrj.br/jspui/handle/jspui/3479 }}

Environmental factors, such as glandular viral infection, could prompt epithelial cells to activate the HLA-independent innate immune system through toll-like receptors.{{cite journal | vauthors = Takeda K, Kaisho T, Akira S | title = Toll-like receptors | journal = Annu. Rev. Immunol. | volume = 21 | pages = 335–76 | date = 2003 | pmid = 12524386 | doi = 10.1146/annurev.immunol.21.120601.141126 }} Although several infectious, exogenous agents have been implicated in the pathogenesis of Sjögren's disease, such as Epstein-Barr virus (EBV), human T-lymphotropic virus 1, and hepatitis C virus, their association with Sjögren's disease appears weak. While EBV is present in the salivary glands of normal individuals, a high incidence of EBV reactivation in Sjögren's patients has been reported with increased levels of EBV DNA. This indicates viral reactivation and the inability of lymphoid infiltrates to control EBV replication in Sjögren's disease, leading to the initiation or perpetuation of an immune response in target organs. Nonetheless, exactly how reactivation of EBV is induced in lesions of patients with Sjögren's disease, and which specific molecular mechanisms are involved in the process of viral reactivation, remain to be clarified.{{cite journal | vauthors = Pflugfelder SC, Crouse CA, Monroy D, Yen M, Rowe M, Atherton SS | title = Epstein-Barr virus and the lacrimal gland pathology of Sjögren's syndrome | journal = Am. J. Pathol. | volume = 143 | issue = 1 | pages = 49–64 | date = July 1993 | pmid = 8391219 | pmc = 1886957 }}

Epithelial cells in Sjögren's disease lesions are active participants in the induction and perpetuation of the inflammatory process. Environmental and hormonal factors, in concert with an appropriate genetic background, are believed to trigger Sjögren's disease, which dysregulates epithelial cells and allows aberrant homing and activation of dendritic cells (DCs), T cells, and B cells.{{cite journal | vauthors = Manoussakis MN, Boiu S, Korkolopoulou P, Kapsogeorgou EK, Kavantzas N, Ziakas P, Patsouris E, Moutsopoulos HM | title = Rates of infiltration by macrophages and dendritic cells and expression of interleukin-18 and interleukin-12 in the chronic inflammatory lesions of Sjögren's syndrome: correlation with certain features of immune hyperactivity and factors associated with high risk of lymphoma development | journal = Arthritis Rheum. | volume = 56 | issue = 12 | pages = 3977–88 | date = December 2007 | pmid = 18050195 | doi = 10.1002/art.23073 | doi-access = free }} Dendritic cells are antigen-presenting cells that process antigen material and present it to other T cells. Following the migration of lymphocytes into the glands in response to chemokines and specific adhesion molecules, T cells interact with epithelial cells. Epithelial cells are further activated by proinflammatory cytokines (IL-1β, IFN-γ, and TNF), which are produced by adjacent T cells. The early accumulation of plasmacytoid dendritic cells in the target tissues, which produce high levels of type 1 IFNs, seems important, as these cells can further dysregulate the immune response through abnormal retention of lymphocytes in the tissues, and their subsequent activation. IFN-α stimulates the production of B-cell activating factor (BAFF) by epithelial cells, DCs, and T cells. BAFF stimulates aberrant B-cell maturation, leading to the emergence of self-reactive B cells, which locally produce autoantibodies, in a germinal centre-like structure (GC-like), which is also the location of lymphomagenesis (origin of lymphoma).

Dysregulation of apoptosis (programmed cell death) is believed to play a role in the pathogenesis of a variety of autoimmune diseases, though its role in Sjögren's disease is controversial. Both the Fas and Fas ligand proteins are overexpressed in primary Sjögren's patients, while expression of BCL-1, which is known to downregulate apoptosis, was found significantly reduced in acinar and ductal epithelial cells of Sjögren's patients compared to healthy people.{{cite journal | vauthors = Ohlsson M, Szodoray P, Loro LL, Johannessen AC, Jonsson R | title = CD40, CD154, Bax and Bcl-2 expression in Sjögren's syndrome salivary glands: a putative anti-apoptotic role during its effector phases | journal = Scand. J. Immunol. | volume = 56 | issue = 6 | pages = 561–71 | date = December 2002 | pmid = 12472667 | doi = 10.1046/j.1365-3083.2002.01168.x| s2cid = 39543376 | doi-access = free }}{{cite journal | vauthors = Ohlsson M, Skarstein K, Bolstad AI, Johannessen AC, Jonsson R | title = Fas-induced apoptosis is a rare event in Sjögren's syndrome | journal = Lab. Invest. | volume = 81 | issue = 1 | pages = 95–105 | date = January 2001 | pmid = 11204278 | doi = 10.1038/labinvest.3780215 | doi-access = free }} In situ studies did not show increased apoptosis among glandular epithelial cells but did show reduced apoptosis among infiltrating mononuclear cells. Reduced apoptosis was also implicated in the accumulation of autoreactive B-cells found in the glands. The relationship of autoantibodies expressed in Sjögren's syndrome with apoptosis is still being researched.

Sex hormones seem to influence humoral and cell-mediated immune response, with estrogen being considered one of the biggest factors responsible for sex-immunologic dimorphism.{{cite journal |vauthors=Cutolo M, Sulli A, Capellino S, Villaggio B, Montagna P, Seriolo B, Straub RH |title=Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. |journal=Lupus |volume=13 |issue=9 |pages=635–8 |year=2004 |pmid=15485092 |doi=10.1191/0961203304lu1094oa|s2cid=23941507 }} Estrogen deficiency appears to play a role in the development of Sjögren's disease.{{cite journal|vauthors=Mavragani CP, Fragoulis GE, Moutsopoulos HM|title=Endocrine alterations in primary Sjögren's disease: an overview|journal=J Autoimmun|volume=39|issue=4|pages=354–8|date=Dec 2012|pmid=22695186|doi=10.1016/j.jaut.2012.05.011|type=Review}} It has been hypothesized that androgen administration to the ocular surface may serve as an effective therapy for dry eyes.{{cite journal |vauthors=Sullivan DA, Wickham LA, Rocha EM, Krenzer KL, Sullivan BD, Steagall R, Cermak JM, Dana MR, Ullman MD, Sato EH, Gao J, Rocha FJ, Ono M, Silveira LA, Lambert RW, Kelleher RS, Tolls DB, Toda I |title=Androgens and dry eye in Sjögren's syndrome |journal=Ann N Y Acad Sci |volume=876 |issue=1 |pages=312–24 |year=1999 |pmid=10415627 |doi=10.1111/j.1749-6632.1999.tb07656.x|bibcode=1999NYASA.876..312S |s2cid=33718591 }}

While Sjögren's disease{{cite web|date=2017-10-23|title=Sjögren's syndrome treatment – NHS|url=https://www.nhs.uk/conditions/sjogrens-syndrome/treatment/|access-date=2020-10-03|website=nhs.uk|language=en}} is one of the most common auto-immune diseases, it has no specific and non-invasive diagnostic tests.

Diagnosing Sjögren's disease (SjD) is complicated by the range of symptoms that a patient may manifest, and the similarity between symptoms of Sjögren's disease and those of other conditions. Also, patients with SS symptoms approach different specialities for treatment, which can make diagnosis difficult. Since dry eyes and dry mouth are very common symptoms, and frequently occur in people over 40, affected people may believe that the symptoms are age-related, so ignore them. Some medications can cause symptoms similar to those of Sjögren's disease.{{cn|date=December 2024}}

The combination of several tests, which can be done in a series, can eventually diagnose Sjögren's disease.{{cite journal | author = Fox R. I. | year = 2005 | title = Sjögren's syndrome | journal = Lancet | volume = 366 | issue = 9482| pages = 321–331 | doi=10.1016/s0140-6736(05)66990-5| pmid = 16039337 | s2cid = 16426363 }}

File:Main antinuclear antibody patterns on immunofluorescence.png patterns on immunofluorescence.{{cite journal| author=Al-Mughales JA| title=Anti-Nuclear Antibodies Patterns in Patients With Systemic Lupus Erythematosus and Their Correlation With Other Diagnostic Immunological Parameters. | journal=Front Immunol | year= 2022 | volume= 13 | issue= | pages= 850759 | pmid=35359932 | doi=10.3389/fimmu.2022.850759 | pmc=8964090 | doi-access=free }}
Minor edits by

Mikael Häggström, MD
- Attribution 4.0 International (CC BY 4.0) license Individuals with Sjögren syndrome usually have a speckled or homogeneous pattern, and rarely a centromere pattern.{{cite web|url=https://www.hopkinssjogrens.org/disease-information/diagnosis-sjogrens-syndrome/blood-and-urine-tests/|title=Blood and Urine Tests|website=Johns Hopkins School of Medicine|access-date=2023-05-28}}]]

Blood tests can be done to determine if a patient has high levels of antibodies that are indicative of the condition, such as antinuclear antibody (ANA) and rheumatoid factor (because Sjögren's disease frequently occurs secondary to rheumatoid arthritis), which are associated with autoimmune diseases. Typical SS ANA patterns are SSA/Ro and SSB/La, of which anti-SSB/La is far more specific; anti-SSA/Ro is associated with numerous other autoimmune conditions, but is often present in SS. However anti-SSA and anti-SSB tests are frequently not positive in SS.{{citation needed|date=October 2020}}

The rose bengal test uses a stain that measures the state and function of the lacrimal glands. This test involves placing the nontoxic dye rose bengal on the eyes. The dye's distinctive colour helps in determining the state and functioning of the tear film and the rate of tear evaporation. Any distinctive colour change can indicate SS, but confirming the condition requires many related diagnostic tools.

Schirmer's test measures the production of tears: a strip of filter paper is held inside the lower eyelid for five minutes, and its wetness is then measured with a ruler. Producing less than {{Convert|5|mm|abbr=on}} of liquid is usually indicative of SS. This measurement analysis varies among people depending on other eye-related conditions and medications in use when the test is taken. A slit-lamp examination can reveal dryness on the surface of the eye.{{citation needed|date=October 2020}}

Use of Schirmer strips to test oral dryness is possible.{{cite journal |last1=Schoppmeier |first1=Christoph Matthias |last2=Helpap |first2=Juliane |last3=Hagemeier |first3=Anna |last4=Wicht |first4=Michael Jochen |last5=Barbe |first5=Anna Greta |title=Using the modified Schirmer test for dry mouth assessment: A cross-sectional study |journal=European Journal of Oral Sciences |date=August 2022 |volume=130 |issue=4 |pages=e12880 |doi=10.1111/eos.12880 |pmid=35692181 |s2cid=249622808 |doi-access=free }}{{cite journal | pmc=8137574 | year=2021 | last1=Wróbel-Dudzińska | first1=D. | last2=Kubik-Komar | first2=A. | last3=Rykwa | first3=D. | last4=Kosior-Jarecka | first4=E. | last5=Żarnowski | first5=T. | last6=Chałas | first6=R. | title=The use of Schirmer strips to measure salivary and lacrimal flow in non-Sjögren patients | journal=Clinical Oral Investigations | volume=25 | issue=6 | pages=4107–4114 | doi=10.1007/s00784-020-03741-3 | pmid=33389133 }}

Symptoms of dry mouth and dryness in the oral cavity are caused by the reduced production of saliva from the salivary glands (parotid gland, submandibular gland, and sublingual gland).

In unstimulated whole saliva flow collection, the person spits into a test tube every minute for approximately 15 minutes. A resultant collection of less than {{Convert|1.5|ml|abbr=on}} is considered a positive result.Dr. J. Parks, Ancaster ON Canada

In a stimulated saliva flow test the person sucks on a sugar-free sweet, whilst collecting saliva. An unstimulated salivary flow rate of 0.1 to 0.2 ml/min and a stimulated flow rate of 0.7 ml/min or less is considered to be abnormally low flow rates indicative of salivary gland hypofunction.{{cite web | url=https://ostrowon.usc.edu/salivary-gland-and-flow-exam/ | title=How to Perform a Salivary Gland and Salivary Flow Exam | date=15 June 2020 }}

Unstimulated saliva production reduces by 40 to 70% between the ages of 20 and 80 years, but stimulated saliva production is not affected.{{cite journal |last1=Lacombe |first1=Valentin |last2=Lacout |first2=Carole |last3=Lozac'h |first3=Pierre |last4=Ghali |first4=Alaa |last5=Gury |first5=Aline |last6=Lavigne |first6=Christian |last7=Urbanski |first7=Geoffrey |title=Unstimulated whole saliva flow for diagnosis of primary Sjögren's disease: time to revisit the threshold? |journal=Arthritis Research & Therapy |date=December 2020 |volume=22 |issue=1 |pages=38 |doi=10.1186/s13075-020-2132-3 |pmid=32093745 |pmc=7041275 |s2cid=211265587 |doi-access=free }}

A lip/salivary gland biopsy takes a tissue sample that can reveal lymphocytes clustered around salivary glands, and damage to these glands from inflammation. This test involves removing a sample of tissue from a person's inner lip/salivary gland and examining it under a microscope. On such biopsies, the single most important test result in the diagnosis of the oral component of Sjögren syndrome is likely the focus score, which is the number of mononuclear cell infiltrates containing at least 50 inflammatory cells in a 4 mm² glandular section.{{cite journal| author=Segerberg-Konttinen M, Konttinen YT, Bergroth V| title=Focus score in the diagnosis of Sjögren's disease. | journal=Scand J Rheumatol Suppl | year= 1986 | volume= 61 | issue= | pages= 47–51 | pmid=3473649 }} The Chisholm-Mason grades are also widely used for salivary gland biopsies (see table).{{cite journal| author=Costa S, Quintin-Roué I, Lesourd A, Jousse-Joulin S, Berthelot JM, Hachulla E | display-authors=etal| title=Reliability of histopathological salivary gland biopsy assessment in Sjögren's syndrome: a multicentre cohort study. | journal=Rheumatology (Oxford) | year= 2015 | volume= 54 | issue= 6 | pages= 1056–64 | pmid=25433039 | doi=10.1093/rheumatology/keu453 | doi-access=free }}

Salivary gland ultrasonography is not invasive and may help reduce unnecessary biopsies in anti-SSA-negative patients.

{{cite journal | url=https://www.sciencedirect.com/science/article/abs/pii/S0720048X23000797 | doi=10.1016/j.ejrad.2023.110765 | title=Diagnostic value of ultrasound evaluation of major salivary glands for Sjögren's disease based on the novel OMERACT scoring system | date=2023 | last1=Tang | first1=Guoxue | last2=Luo | first2=Yi | last3=Mo | first3=Yingqian | last4=Yao | first4=Jiyi | last5=Yang | first5=Haiyun | last6=Hao | first6=Shaoyun | journal=European Journal of Radiology | volume=162 | pmid=36893528 | s2cid=257370253 }}{{cite web | url=https://sjogrenssyndromenews.com/news/salivary-gland-ultrasound-may-help-diagnose-study-effective/?preview_id=72789 | title=Salivary gland ultrasound may help diagnose Sjögren's disease: Study | Ultrasound may be as effective as salivary gland biopsy for diagnosis: Study | Sjogren's Syndrome News | date=10 March 2023 }}{{cite journal | pmc=9444027 | date=2022 | last1=Lorenzon | first1=M. | last2=Spina | first2=E. | last3=Tulipano Di Franco | first3=F. | last4=Giovannini | first4=I. | last5=De Vita | first5=S. | last6=Zabotti | first6=A. | title=Salivary Gland Ultrasound in Primary Sjögren's Syndrome: Current and Future Perspectives | journal=Open Access Rheumatology: Research and Reviews | volume=14 | pages=147–160 | doi=10.2147/OARRR.S284763 | pmid=36072437 | doi-access=free }}{{cite web | url=https://www.niams.nih.gov/health-topics/sjogrens-syndrome/diagnosis-treatment-and-steps-to-take#:~:text=Ultrasound%20imaging%20and%20biopsy%20can,syndrome%20and%20other%20autoimmune%20disorders | title=Sjögren's Syndrome | work=National Institute of Arthritis and Musculoskeletal and Skin Diseases | date=7 April 2017 }}

A radiological procedure is available as a reliable and accurate test for Sjögren's disease, in the form of a sialogram. A contrast agent is injected into the parotid duct, which opens from the cheek into the vestibule of the mouth opposite the neck of the upper second molar tooth. The test is intended to detect any blockage in the salivary gland ducts (i.e. parotid duct) and the amount of saliva that flows into the mouth.

For Sjögren's disease, sudomotor function through electrochemical skin conductance may help in the diagnosis process.{{cite journal |last1=Zouari |first1=Hela G. |last2=Wahab |first2=Abir |last3=Ng Wing Tin |first3=Sophie |last4=Sène |first4=Damien |last5=Lefaucheur |first5=Jean-Pascal |title=The Clinical Features of Painful Small-Fiber Neuropathy Suggesting an Origin Linked to Primary Sjögren's Syndrome |journal=Pain Practice |date=April 2019 |volume=19 |issue=4 |pages=426–434 |doi=10.1111/papr.12763 |pmid=30636091 |s2cid=58646701 }}{{cite journal |last1=Ng Wing Tin |first1=Sophie |last2=Zouari |first2=Hela G |last3=Wahab |first3=Abir |last4=Sène |first4=Damien |last5=Lefaucheur |first5=Jean-Pascal |title=Characterization of Neuropathic Pain in Primary Sjögren's Syndrome with Respect to Neurophysiological Evidence of Small-Fiber Neuropathy |journal=Pain Medicine |date=1 May 2019 |volume=20 |issue=5 |pages=979–987 |doi=10.1093/pm/pny183 |pmid=30247738 }}

People with Sjögren's may also have other autoimmune conditions.{{cite web | url=https://academic.oup.com/rheumap/article/7/2/rkad030/7115846 | doi=10.1093/rap/rkad030 | title=Autoimmune comorbidities associated with sarcoidosis: A case-control study in the All of Us research program | date=2023 | journal=Rheumatology Advances in Practice | volume=7 | issue=2 | pages=rkad030 | pmid=38606002 | pmc=11007907 | vauthors = Murphy MJ, Edemobi P, Leasure AC, Gulati M, Miller EJ, Damsky W, Cohen JM }}{{cite journal | url=https://pubmed.ncbi.nlm.nih.gov/30226016/ | pmid=30226016 | date=2019 | last1=Bao | first1=Y. K. | last2=Weide | first2=L. G. | last3=Ganesan | first3=V. C. | last4=Jakhar | first4=I. | last5=McGill | first5=J. B. | last6=Sahil | first6=S. | last7=Cheng | first7=A. L. | last8=Gaddis | first8=M. | last9=Drees | first9=B. M. | title=High prevalence of comorbid autoimmune diseases in adults with type 1 diabetes from the HealthFacts database | journal=Journal of Diabetes | volume=11 | issue=4 | pages=273–279 | doi=10.1111/1753-0407.12856 | s2cid=52287975 }}{{cite web | url=https://www.autoimmuneinstitute.org/articles/about-autoimmune/comorbidities-multiple-autoimmune-syndrome/ | archive-url=https://web.archive.org/web/20230606101851/https://www.autoimmuneinstitute.org/articles/about-autoimmune/comorbidities-multiple-autoimmune-syndrome/ | url-status=dead | archive-date=June 6, 2023 | title=Comorbidities in Autoimmune Disease & Multiple Autoimmune Syndrome | work=Global Autoimmune Institute | date=29 December 2022 | vauthors = Serraino C }}

Sjögren's disease may be excluded in people with past head and neck radiation therapy, acquired immunodeficiency syndrome, pre-existing lymphoma, sarcoidosis, graft-versus-host disease, and use of anticholinergic drugs.{{citation needed|date=December 2020}}

No prevention mechanism exists for Sjögren's disease (SjD) because of its complexity as an autoimmune disorder. However, lifestyle changes can reduce the risk factors related to developing SS or reducing the severity of the condition for patients who have already been diagnosed.{{Citation needed|date=December 2022}}

Diet is strongly associated with the inflammation seen in many autoimmune-related diseases, including SS. An experimental study concluded that SS patients often show high sensitivity to gluten that directly relates to inflammation.{{cite journal | vauthors = Lidén M, Kristjánsson G, Valtýsdóttir S, Hällgren R | title = Gluten sensitivity in patients with primary Sjögren's syndrome | journal = Scand. J. Gastroenterol. | volume = 42 | issue = 8 | pages = 962–7 | date = August 2007 | pmid = 17613926 | doi = 10.1080/00365520701195345 | s2cid = 26333122 }}

Moderate exercise is also helpful in SS patients, mainly reducing the effect of lung inflammation.{{cite journal | vauthors = Strömbeck BE, Theander E, Jacobsson LT | title = Effects of exercise on aerobic capacity and fatigue in women with primary Sjogren's syndrome | journal = Rheumatology (Oxford) | volume = 46 | issue = 5 | pages = 868–71 | date = May 2007 | pmid = 17308315 | doi = 10.1093/rheumatology/kem004 | doi-access = free }}{{Citation needed|reason=The referenced study found that physical activity increased aerobic capacity and reduced fatigue (when measured by VAS); however, it makes no claims about lung inflammation. |date=March 2021}}

Treatment is directed at managing the person's symptoms. For dry eyes, artificial tears; medications to reduce inflammation; punctal plugs or other surgery to shut the tear ducts may be tried. For a dry mouth, chewing gum (preferably sugar-free); sipping water; or a saliva substitute may be used. In those with joint or muscle pain, ibuprofen may be used. Medications that can cause dryness, such as antihistamines, may also be stopped. The most specific extant diagnostic test requires lip biopsy.{{Cite journal |last1=Giovelli |first1=Raquel A |last2=Santos |first2=Maria CS |last3=Serrano |first3=Érica V |last4=Valim |first4=Valéria |date=2015-02-15 |title=Clinical characteristics and biopsy accuracy in suspected cases of Sjögren's disease referred to labial salivary gland biopsy |journal=BMC Musculoskelet Disord |volume=16 |pages=Article 30 |doi=10.1186/s12891-015-0482-9 |doi-access=free |pmc=4332430 }}

Neither a cure nor a specific treatment for Sjögren's disease is known to permanently restore gland secretion. Instead, treatment is generally symptomatic and supportive.{{cite web |title=Sjogren syndrome: MedlinePlus Medical Encyclopedia |url=https://medlineplus.gov/ency/article/000456.htm |access-date=2022-11-18 |website=medlineplus.gov |language=en}}{{cite web |title=Sjogren's Syndrome |url=https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Sjogrens-Syndrome |access-date=2022-11-18 |website=www.rheumatology.org}}

Moisture replacement therapies such as artificial tears may ease the symptoms of dry eyes. Some patients with more severe problems use goggles to increase local humidity or have punctal plugs inserted to help retain tears on the ocular surface for a longer time.{{Cite web |last=Branch |first=NIAMS Science Communications and Outreach |date=2017-04-07 |title=Sjögren's Syndrome |url=https://www.niams.nih.gov/health-topics/sjogrens-syndrome |access-date=2024-03-11 |website=National Institute of Arthritis and Musculoskeletal and Skin Diseases |language=en}}

Additionally, cyclosporine (Restasis) is available by prescription to treat chronic dry eye by suppressing the inflammation that disrupts tear secretion. Prescription drugs are also available that help to stimulate salivary flow, such as cevimeline (Evoxac) and pilocarpine. Salagen, a manufactured form of pilocarpine, can be used to help produce tears, as well as saliva in the mouth and intestines.{{cite journal |last1=Vivino |first1=Frederick B. |title=The treatment of Sjögren's syndrome patients with Pilocarpine-tablets |journal=Scandinavian Journal of Rheumatology |date=2009 |volume=30 |issue=115 |pages=1–13 |doi=10.1080/030097401300232583 |pmid=11469515 |s2cid=21260961 }} It is derived from the jaborandi plant.{{cite journal |last1=de Abreu |first1=Ilka Nacif |title=Production of pilocarpine in callus of jaborandi (pilocarpus microphyllus stapf) |journal=In Vitro Cellular & Developmental Biology – Plant |date=2005 |volume=41 |issue=6 |pages=806–811 |doi=10.1079/IVP2005711 |s2cid=26058596 }}

In women with Sjögren's disease, vaginal dryness, vulvodynia and dyspareunia (painful sexual intercourse) are often reported; personal lubricants are recommended to help lessen irritation or pain that may result from dryness in the vaginal and vulval areas.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed, and sometimes intravenous immunoglobulins. Also, disease-modifying antirheumatic drugs such as methotrexate may be helpful. Hydroxychloroquine (Plaquenil) is another option and is generally considered safer than methotrexate. However, these prescribed drugs have a range of side effects such as nausea, loss of appetite, dizziness, hair loss, stomach aches/cramps, headache, liver toxicity and increased risk of infections.{{cn|date=December 2024}}

For systemic symptoms, including fatigue, joint pain, myositis, and neuropathy, biologic immunosuppressant drugs such as rituximab and belimumab that work via B-cell pathology are often used and have less toxic profiles than traditional immunosuppressive regimens.{{citation needed|date=October 2020}}

Preventive dental treatment is also necessary (and often overlooked by the patient), as the lack of saliva associated with xerostomia creates an ideal environment for the proliferation of bacteria that cause cavities.{{cite journal | last1 = Xin | first1 = W | last2 = Leung | first2 = KC | last3 = Lo | first3 = EC | last4 = Mok | first4 = MY | last5 = Leung | first5 = MH | year = 2016| title = A randomized, double-blind, placebo-controlled clinical trial of fluoride varnish in preventing dental caries of Sjögren's disease patients | journal = BMC Oral Health | volume = 16 | issue = 1| page = 102 | doi = 10.1186/s12903-016-0296-7 | pmc = 5034648 | pmid = 27664129 | doi-access = free }} Treatments include at-home topical fluoride application to strengthen tooth enamel and frequent teeth cleanings by a dental hygienist. Existing cavities must also be treated, as cavities that extend into the tooth cannot be effectively treated by teeth cleaning alone, and are at a high risk of spreading into the pulp of the tooth, leading to the loss of vitality and need for extraction or root canal therapy. This treatment regimen is the same as for all xerostomia patients, such as for those undergoing head and neck radiation therapy, which often damages the salivary glands; these glands are more susceptible to radiation than other body tissues.{{citation needed|date=October 2020}}

Fatigue, depression, and aerobic capacity all showed a significant difference after a 12-week exercise program compared with controls, in favor of the exercise intervention.{{Cite journal |last1=Strömbeck |first1=B. E. |last2=Theander |first2=E. |last3=Jacobsson |first3=L. T. H. |date=May 2007 |title=Effects of exercise on aerobic capacity and fatigue in women with primary Sjogren's syndrome |url=https://pubmed.ncbi.nlm.nih.gov/17308315 |journal=Rheumatology |volume=46 |issue=5 |pages=868–871 |doi=10.1093/rheumatology/kem004 |issn=1462-0324 |pmid=17308315}} A small study showed possible efficacy of vagus nerve stimulation for Sjogren's fatigue reduction.{{cite journal |last1=Tarn |first1=Jessica |last2=Evans |first2=Evelyn |last3=Traianos |first3=Emmanuella |last4=Collins |first4=Alexis |last5=Stylianou |first5=Mryto |last6=Parikh |first6=Jehill |last7=Bai |first7=Yang |last8=Guan |first8=Yu |last9=Frith |first9=James |last10=Lendrem |first10=Dennis |last11=Macrae |first11=Victoria |last12=McKinnon |first12=Iain |last13=Simon |first13=Bruce S. |last14=Blake |first14=Justyna |last15=Baker |first15=Mark R. |last16=Taylor |first16=John Paul |last17=Watson |first17=Stuart |last18=Gallagher |first18=Peter |last19=Blamire |first19=Andrew |last20=Newton |first20=Julia |last21=Ng |first21=Wan-Fai |title=The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue in Participants With Primary Sjögren's Syndrome |journal=Neuromodulation: Technology at the Neural Interface |date=1 April 2023 |volume=26 |issue=3 |pages=681–689 |doi=10.1016/j.neurom.2022.08.461 |pmid=37032583 |s2cid=253172246 |issn=1094-7159|doi-access=free }}

Results from a number of studies indicate that, compared to other autoimmune diseases, Sjögren's disease is associated with a notably high incidence of non-Hodgkin lymphoma, a cancer of white blood cells. About 5% of patients with SS develop some form of lymphoid malignancy.{{cite journal|title=Update on Sjögren's syndrome autoimmune epithelitis: from classification to increased neoplasias |journal=Best Pract Res Clin Rheumatol |volume=21 |issue=6 |pages=989–1010 |year=2007 |pmid=18068857 |doi=10.1016/j.berh.2007.09.001|last1=Tzioufas|first1=Athanasios G.|last2=Voulgarelis|first2=Michael}} Patients with severe cases are much more likely to develop lymphomas than patients with mild or moderate cases. The most common lymphomas are salivary extranodal marginal zone B cell lymphomas (MALT lymphomas in the salivary glands){{cite journal |title=Clinical, immunologic, and molecular factors predicting lymphoma development in Sjogren's syndrome patients |journal=Clin Rev Allergy Immunol |volume=32 |issue=3 |pages=265–74 |year=2007 |pmid=17992593 |doi=10.1007/s12016-007-8001-x |last1=Voulgarelis |first1=Michael |last2=Skopouli |first2=Fotini N.|s2cid=19070113 }} and diffuse large B-cell lymphoma.{{cite journal|title=Malignant lymphomas in autoimmunity and inflammation: a review of risks, risk factors, and lymphoma characteristics |journal=Cancer Epidemiol. Biomarkers Prev. |volume=15 |issue=11 |pages=2069–77 |year=2006 |pmid=17119030 |doi=10.1158/1055-9965.EPI-06-0300|last1=Smedby|first1=K. E.|last2=Baecklund|first2=E.|last3=Askling|first3=J.|doi-access=free}}

Lymphomagenesis in primary Sjögren's disease patients is considered a multistep process, with the first step being chronic stimulation of autoimmune B cells, especially B cells that produce rheumatoid factor at sites targeted by the disease.{{cite journal | vauthors = Martin T, Weber JC, Levallois H, Labouret N, Soley A, Koenig S, Korganow AS, Pasquali JL | title = Salivary gland lymphomas in patients with Sjögren's syndrome may frequently develop from rheumatoid factor B cells | journal = Arthritis Rheum. | volume = 43 | issue = 4 | pages = 908–16 | date = April 2000 | pmid = 10765938 | doi = 10.1002/1529-0131(200004)43:4<908::AID-ANR24>3.0.CO;2-K | doi-access = free }}{{cite journal | vauthors = Bende RJ, Aarts WM, Riedl RG, de Jong D, Pals ST, van Noesel CJ | title = Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity | journal = J. Exp. Med. | volume = 201 | issue = 8 | pages = 1229–41 | date = April 2005 | pmid = 15837810 | pmc = 2213160 | doi = 10.1084/jem.20050068 }} This increases the frequency of oncogenic mutation, leading to any dysfunction at checkpoints of autoimmune B-cell activation to transform into malignancy. A study's finding has concluded the continuous stimulation of autoimmune B cells, leads to subtle germinal abnormalities in genes having specific consequences in B cells, which underlies the susceptibility to lymphoma.{{cite journal |last1=Nocturne |first1=G. |last2=Boudaoud |first2=S. |last3=Miceli Richard |first3=C. |last4=Viengchareun |first4=S. |last5=Lazure |first5=T. |last6=Nititham |first6=J. |last7=Taylor |first7=K. E. |last8=Criswell |first8=L. A. |last9=Ma |first9=A. |last10=Busato |first10=F. |last11=Melki |first11=J. |last12=Dubost |first12=J. J. |last13=Hachulla |first13=E. |last14=Gottenberg |first14=J. E. |last15=Lombes |first15=M. |last16=Tost |first16=J. |last17=Mariette |first17=X. |title=OP0023 Germinal and Somatic Genetic Variants of TNFAIP3 Promote Lymphomagenesis Process Complicating Primary Sjögren's Syndrome |journal=Annals of the Rheumatic Diseases |date=June 2013 |volume=72 |issue=Suppl 3 |pages=A55.3–A56 |doi=10.1136/annrheumdis-2013-eular.228 |s2cid=75620379 }}

Apart from the notably higher incidence of malignant NHL, Sjögren's patients show only modest or clinically insignificant deterioration in specific organ-related function.{{cn|date=December 2024}}

Sjögren's disease is associated with a high burden of illness,{{cite journal |last1=Vivino |first1=Frederick B. |title=Sjogren's syndrome: Clinical aspects |journal=Clinical Immunology |date=September 2017 |volume=182 |pages=48–54 |doi=10.1016/j.clim.2017.04.005 |pmid=28428095 }} and has been shown to markedly reduce quality of life (QoL),{{cite web | url=https://www.sjogrens.org/understanding-sjogrens/resources/patient-survey-results | title=Patient Survey Results }} with a significant impact on ability to work resulting from increased rates of disability.{{cite journal |last1=Meijer |first1=Jiska M. |last2=Meiners |first2=Petra M. |last3=Huddleston Slater |first3=James J. R. |last4=Spijkervet |first4=Fred K. L. |last5=Kallenberg |first5=Cees G. M. |last6=Vissink |first6=Arjan |last7=Bootsma |first7=Hendrika |title=Health-related quality of life, employment and disability in patients with Sjögren's disease |journal=Rheumatology |date=September 2009 |volume=48 |issue=9 |pages=1077–1082 |doi=10.1093/rheumatology/kep141 |pmid=19553376 }}{{cite journal |last1=Miyamoto |first1=Samira T |last2=Valim |first2=Valéria |last3=Fisher |first3=Benjamin A |title=Health-related quality of life and costs in Sjögren's syndrome |journal=Rheumatology |date=18 June 2021 |volume=60 |issue=6 |pages=2588–2601 |doi=10.1093/rheumatology/key370 |pmid=30770918 |url=http://pure-oai.bham.ac.uk/ws/files/54982264/HRQoL_and_cost_revised_v2_final_clean_with_figures.pdf }}{{cite journal |last1=Zhang |first1=Qiuxiang |last2=Wang |first2=Xulin |last3=Chen |first3=Haoyang |last4=Shen |first4=Biyu |title=Sjögren's syndrome is associated with negatively variable impacts on domains of health-related quality of life: evidence from Short Form 36 questionnaire and a meta-analysis |journal=Patient Preference and Adherence |date=10 May 2017 |volume=11 |pages=905–911 |doi=10.2147/PPA.S132751 |pmid=28546741 |pmc=5436777 |doi-access=free }} The reduction in QoL is similar to that seen in other chronic conditions such as rheumatoid arthritis, lupus and fibromyalgia.

Published studies on the survival of Sjögren's disease patients have been limited in varied respects, perhaps owing to the relatively small sample sizes and the fact that secondary Sjögren's disease is associated with other autoimmune diseases.

A 2010 study found a slight increase in mortality rates of Sjögren's patients in comparison with the remainder of the population. A 2016 study found that primary Sjögren's was not associated with an increase in all-cause mortality as compared with the general population, but that a subset of patients with extraglandular involvement, vasculitis, hypocomplementaemia, and cryoglobulinaemia may be at increased risk of mortality.{{cite journal |last1=Singh |first1=Abha G. |last2=Singh |first2=Siddharth |last3=Matteson |first3=Eric L. |title=Rate, risk factors and causes of mortality in patients with Sjögren's syndrome: a systematic review and meta-analysis of cohort studies |journal=Rheumatology |date=27 September 2015 |volume=55 |issue=3 |pages=450–460 |doi=10.1093/rheumatology/kev354 |pmid=26412810 |pmc=5009445 |doi-access=free }} A 2021 metaanalysis showed a 46% increase in mortality, with significantly greater mortality risk in patients with older age, male gender, vasculitis, interstitial lung disease, low complements, positive anti-La/SSB and cryoglobulinaemia.{{cite journal |last1=Huang |first1=Hong |last2=Xie |first2=Wenhui |last3=Geng |first3=Yan |last4=Fan |first4=Yong |last5=Zhang |first5=Zhuoli |title=Mortality in patients with primary Sjögren's syndrome: a systematic review and meta-analysis |journal=Rheumatology |date=1 September 2021 |volume=60 |issue=9 |pages=4029–4038 |doi=10.1093/rheumatology/keab364 |pmid=33878179 }}

Among those without other autoimmune disorders, life expectancy is unchanged.{{cite journal| last1= Singh| first1=AG|last2=Singh|first2=S|last3=Matteson|first3=EL|date=March 2016|title=Rate, risk factors and causes of mortality in patients with Sjögren's syndrome: a systematic review and meta-analysis of cohort studies |journal= Rheumatology| volume= 55| issue= 3| pages=450–60|doi=10.1093/rheumatology/kev354|pmid=26412810|pmc=5009445}}

Sjögren's disease (SjD) is the third-most common rheumatic autoimmune disorder, behind rheumatoid arthritis and systemic lupus erythematosus.{{cite journal | vauthors = Fox RI, Stern M, Michelson P | title = Update in Sjögren syndrome | journal = Curr Opin Rheumatol | volume = 12 | issue = 5 | pages = 391–8 | date = September 2000 | pmid = 10990175 | doi = 10.1097/00002281-200009000-00007 }}

There are no geographical differences in the rates of SS.{{cite journal | author = Mavragani C. P., Moutsopoulos H. M. | year = 2010 | title = The geoepidemiology of Sjogren's syndrome | journal = Autoimmunity Reviews | volume = 9 | issue = 5| pages = A305–A310 | doi=10.1016/j.autrev.2009.11.004 | pmid=19903539}} Sjögren's syndrome has been reported in all areas of the world, although regional rates have not been well studied.

Depending on the criteria for determining prevalence, studies estimate the prevalence of SS at between 500,000 and two million people in the United States. Broader studies of SS prevalence range widely, with some reports of up to a prevalence of 3% of the population. A few studies have reported that the incidence of the syndrome varies between three and six per 100,000 per year.{{cite journal | vauthors = Alamanos Y, Tsifetaki N, Voulgari PV, Venetsanopoulou AI, Siozos C, Drosos AA | title = Epidemiology of primary Sjögren's syndrome in north-west Greece, 1982–2003 | journal = Rheumatology (Oxford) | volume = 45 | issue = 2 | pages = 187–91 | date = February 2006 | pmid = 16332955 | doi = 10.1093/rheumatology/kei107 | doi-access = free }}

Between 0.2 and 1.2% of the population is affected, with half having the primary form and half the secondary form. It is around 10 times more common in women than in men. Though the disease commonly begins in middle age, people of any age can be affected.

Nine out of 10 SjD patients are women.{{cite journal | vauthors = Jonsson R, Vogelsang P, Volchenkov R, Espinosa A, Wahren-Herlenius M, Appel S | title = The complexity of Sjögren's syndrome: novel aspects on pathogenesis | journal = Immunol. Lett. | volume = 141 | issue = 1 | pages = 1–9 | date = December 2011 | pmid = 21777618 | doi = 10.1016/j.imlet.2011.06.007 }} In addition to prevalence in women, having a first-degree relative with an autoimmune disease and previous pregnancies have been identified as epidemiological risk factors.{{cite journal | vauthors = Priori R, Medda E, Conti F, Cassarà EA, Sabbadini MG, Antonioli CM, Gerli R, Danieli MG, Giacomelli R, Pietrogrande M, Valesini G, Stazi MA | title = Risk factors for Sjögren's syndrome: a case-control study | journal = Clin. Exp. Rheumatol. | volume = 25 | issue = 3 | pages = 378–84 | date = 2007 | pmid = 17631733 }} Despite the lower risk for men, primary SS in men tends to represent a more severe form of the disease.{{cite journal |last1=Ramírez Sepúlveda |first1=Jorge I. |last2=Kvarnström |first2=Marika |last3=Brauner |first3=Susanna |last4=Baldini |first4=Chiara |last5=Wahren-Herlenius |first5=Marie |title=Difference in clinical presentation between women and men in incident primary Sjögren's syndrome |journal=Biology of Sex Differences |date=December 2017 |volume=8 |issue=1 |pages=16 |doi=10.1186/s13293-017-0137-7 |pmid=28507729 |pmc=5427625 |s2cid=2500540 |doi-access=free }} The role of race and ethnicity in the prevalence of the disease is unknown.{{citation needed|date=October 2020}}

Although Sjögren's disease occurs in all age groups, the average age of onset is between ages 40 and 60, although as many as half of all cases may be left undiagnosed or unreported.{{cite journal | vauthors = Haugen AJ, Peen E, Hultén B, Johannessen AC, Brun JG, Halse AK, Haga HJ | title = Estimation of the prevalence of primary Sjögren's syndrome in two age-different community-based populations using two sets of classification criteria: the Hordaland Health Study | journal = Scand. J. Rheumatol. | volume = 37 | issue = 1 | pages = 30–4 | date = 2008 | pmid = 18189192 | doi = 10.1080/03009740701678712 | s2cid = 42392790 }}{{cite journal | vauthors = García-Carrasco M, Ramos-Casals M, Rosas J, Pallarés L, Calvo-Alen J, Cervera R, Font J, Ingelmo M | title = Primary Sjögren syndrome: clinical and immunologic disease patterns in a cohort of 400 patients | journal = Medicine (Baltimore) | volume = 81 | issue = 4 | pages = 270–80 | date = July 2002 | pmid = 12169882 | doi = 10.1097/00005792-200207000-00003 | s2cid = 8279532 | doi-access = free }} The prevalence of SS generally increases with age.

Sjögren's disease is reported in 30-50% of people with rheumatoid arthritis and in 10-25% with systemic lupus erythematosus.

The disease was described in 1933 by Henrik Sjögren, after whom it is named, but a number of earlier descriptions of people with the symptoms exist.

Jan Mikulicz-Radecki (1850–1905) is generally credited with the first description of SS. In 1892, he described a 42-year-old man with enlargement of the parotid and lacrimal glands associated with a round-cell infiltrate and acinar atrophy.{{cite journal | vauthors = Parke AL, Buchanan WW | title = Sjögren's syndrome: History, clinical and pathological features | journal = Inflammopharmacology | volume = 6 | issue = 4 | pages = 271–87 | date = 1998 | pmid = 17657625 | doi = 10.1007/s10787-998-0012-6 | s2cid = 12580734 }} However, the criteria that Mikulicz established for diagnosis often led to misdiagnosis of Mikulicz's syndrome. Many conditions, such as tuberculosis, infections, sarcoidosis, and lymphoma present with similar conditions to those ascribed to Mikulicz's syndrome. Nevertheless, the term "Mikulicz's syndrome" is still used occasionally to describe the appearance of lymphocytic infiltrates 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.Murube, J. Henrik Sjögren, 1899–1986. The ocular surface 8, 2–2 (2010) Sjögren introduced the term keratoconjunctivitis sicca for the symptom of dry eyes (keratoconjunctivitis). In 1933, he published his doctoral thesis describing 19 females, most of whom were postmenopausal and had arthritis, showing clinical and pathological manifestations of the syndrome. Sjögren clarified that keratoconjunctivitis sicca, resulting from water deficiency, had no relation to xerophthalmia, resulting from vitamin A deficiency. Sjögren's thesis was not well received as the Board of Examiners criticized some clinical aspects.

After extensive research and data collection, Sjögren published an essential paper in 1951, describing 80 patients with keratoconjunctivitis sicca, 50 of whom also had arthritis. His subsequent follow-up conference trips pertaining to his paper led to an international interest in Sjögren's syndrome. The term "keratoconjunctivitis sicca" was coined by Sjögren himself and began to be identified as Sjögren's syndrome in literature, although it can now have more general usage.

File:Carrie Ann Inaba.jpg is the national awareness ambassador and spokesperson for the Sjögren's Syndrome Foundation.]]

Research into multifactorial autoimmune diseases such as SS focuses on expanding the knowledge surrounding the disorder, improving diagnostic tools and finding ways to prevent, manage and cure the disorder. The United Kingdom Primary Sjögren's Syndrome Registry, a tissue biobank of samples taken for research, supported by the Medical Research Council, UK, was established in 2010. It supports clinical trials and genetic studies of Sjögren's syndrome and is open to those wishing to participate in research studies and to researchers studying the disease.{{cite journal|last1=Ng|first1=W.-F.|last2=Bowman|first2=S. J.|last3=Griffiths|first3=B.|date=January 2011|title=United Kingdom Primary Sjogren's Syndrome Registry—a united effort to tackle an orphan rheumatic disease|journal=Rheumatology (Oxford)|volume=50|issue=1|pages=32–9|doi=10.1093/rheumatology/keq240|pmid=20693261|doi-access=free}}

As with other autoimmune diseases, susceptibility to Sjögren's disease is greatly influenced by the human leukocyte antigen.{{cite journal |title=Genetics of Sjögren's syndrome in the genome-wide association era |journal=J. Autoimmun. |volume=39 |issue=1–2 |pages=57–63 |date=August 2012 |pmid=22289719 |doi=10.1016/j.jaut.2012.01.008 |pmc=3518871 |last1=Ice |first1=John A. |last2=Li |first2=He |last3=Adrianto |first3=Indra |last4=Lin |first4=Paul Chee |last5=Kelly |first5=Jennifer A. |last6=Montgomery |first6=Courtney G. |last7=Lessard |first7=Christopher J. |last8=Moser |first8=Kathy L.}} DQA1*05:01, DQB1*02:01, and DRB1*03:01 alleles were identified as risk factors, while DQA1*02:01, DQA1*03:01 and DQB1*05:01 alleles were found to be protective factors for the disease.{{cite journal |title=HLA and Sjögren's syndrome susceptibility. A meta-analysis of worldwide studies |journal=Autoimmun Rev |volume=11 |issue=4 |pages=281–7 |date=February 2012 |pmid=22001416 |doi=10.1016/j.autrev.2011.10.002 |last1=Cruz-Tapias |first1=Paola |last2=Rojas-Villarraga |first2=Adriana |last3=Maier-Moore |first3=Shannon |last4=Anaya |first4=Juan-Manuel}} The relationship between alleles and specific race was also established.{{cite journal |title=Sjögren's syndrome, the old and the new |journal=Best Pract Res Clin Rheumatol |volume=26 |issue=1 |pages=105–17 |date=February 2012 |pmid=22424197 |doi=10.1016/j.berh.2012.01.012 |last1=Peri |first1=Yogev |last2=Agmon-Levin |first2=Nancy |last3=Theodor |first3=Emanuel |last4=Shoenfeld |first4=Yehuda}} HLA-DQ2 and HLA-B8 are generally found in Caucasian patients, while HLA-DR5 is related to Greek and Israeli patients. Multiple genome-wide association scans may be conducted in the future to identify key risk variants.

Viruses that have been associated with Sjögren's disease include human T-lymphotropic virus type 1 (HTLV-1), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), hepatitis delta virus (HDV) and hepatitis C virus (HCV).{{cite journal |last1=Igoe |first1=Ann |last2=Scofield |first2=R. Hal |title=Autoimmunity and infection in Sjögren's syndrome |journal=Current Opinion in Rheumatology |date=July 2013 |volume=25 |issue=4 |pages=480–487 |doi=10.1097/BOR.0b013e32836200d2 |pmid=23719365 |pmc=4410971 }}{{cite journal |last1=Weller |first1=Melodie L. |last2=Gardener |first2=Matthew R. |last3=Bogus |first3=Zoe C. |last4=Smith |first4=Michael A. |last5=Astorri |first5=Elisa |last6=Michael |first6=Drew G. |last7=Michael |first7=Donald A. |last8=Zheng |first8=Changyu |last9=Burbelo |first9=Peter D. |last10=Lai |first10=Zhennan |last11=Wilson |first11=Paul A. |last12=Swaim |first12=William |last13=Handelman |first13=Beverly |last14=Afione |first14=Sandra A. |last15=Bombardieri |first15=Michele |last16=Chiorini |first16=John A. |title=Hepatitis Delta Virus Detected in Salivary Glands of Sjögren's Syndrome Patients and Recapitulates a Sjögren's Syndrome-Like Phenotype in Vivo |journal=Pathogens and Immunity |date=23 May 2016 |volume=1 |issue=1 |pages=12–40 |doi=10.20411/pai.v1i1.72 |pmid=27294212 |pmc=4902173 |s2cid=13763999 |doi-access=free }}

Some research has shown that a paucity of vitamin A and vitamin D are associated with the disease. Vitamin D deficiency was found to be related to neurological manifestations and the presence of lymphoma among patients, but vitamin A levels were inversely associated with extraglandular manifestations of the disease.

Saliva is a potential diagnostic tool for Sjögren's disease because the salivary component is changed after the onset of the disease.{{cite journal |title=Saliva: a potential media for disease diagnostics and monitoring |journal=Oral Oncol. |volume=48 |issue=7 |pages=569–77 |date=July 2012 |pmid=22349278 |doi=10.1016/j.oraloncology.2012.01.021 |last1=Liu |first1=Jingyi |last2=Duan |first2=Yixiang}} With the new miniaturization technology, called lab on a chip, the diagnosis can be more convenient.

Concerning therapeutics, multiple monoclonal antibodies were under investigation in 2007.{{cite journal |title=The future of biologic agents in the treatment of Sjögren's syndrome |journal=Clin Rev Allergy Immunol |volume=32 |issue=3 |pages=292–7 |date=June 2007 |pmid=17992596 |pmc=2071970 |doi=10.1007/s12016-007-8005-6 |last1=Meijer |first1=Jiska M. |last2=Pijpe |first2=Justin |last3=Bootsma |first3=Hendrika |last4=Vissink |first4=Arjan |last5=Kallenberg |first5=Cees G. M.}} The most promising seemed to be the anti-CD20 rituximab and the anti-CD22 epratuzumab, while the anti-TNF-α and IFN-α seemed less effective.

In 2014, the Sjögren's Foundation (previously the Sjögren's Syndrome Foundation) announced a five-year goal to halve the disease's average time to diagnosis.{{cite web |url=https://www.sjogrens.org/home/about-the-foundation/breakthrough-goal- |publisher=Sjögren's Syndrome Foundation |title="Breakthrough Goal" SSF Launches 5-Year Breakthrough Goal/"To shorten the time to diagnose Sjögren's by 50% in 5 years!" |date=August 2016 |url-status=live |archive-url=https://web.archive.org/web/20140813143225/https://www.sjogrens.org/home/about-the-foundation/breakthrough-goal- |archive-date=13 August 2014 }}

• Shannon Boxx (U.S. Olympic soccer player) has both Sjögren's disease and lupus.{{cite web |url=http://www.cnn.com/2012/08/16/health/olympic-soccer-boxx-lupus/ |title=Olympic soccer player Shannon Boxx's battle with lupus |publisher=CNN |date=2012 |access-date=18 February 2014 |url-status=live |archive-url=https://web.archive.org/web/20140222145320/http://www.cnn.com/2012/08/16/health/olympic-soccer-boxx-lupus/ |archive-date=22 February 2014 }}
• Carrie Ann Inaba (singer-actress) is the national awareness ambassador and spokesperson for the Sjögren's Foundation (previously the Sjögren's Syndrome Foundation).{{cite web|url=https://magazine.medlineplus.gov/article/carrie-ann-inaba-doesnt-let-sjogrens-syndrome-stand-in-her-way|archive-url=https://web.archive.org/web/20211113230511/https://magazine.medlineplus.gov/article/carrie-ann-inaba-doesnt-let-sjogrens-syndrome-stand-in-her-way |url-status=live |title=Carrie Ann Inaba doesn't let Sjögren's syndrome stand in her way|archive-date=November 13, 2021|website=MedlinePlus}}
• Venus Williams (world champion tennis player) has been diagnosed with Sjögren's disease and said she had struggled with fatigue for years.{{cite news |url=https://www.nytimes.com/2011/09/02/sports/tennis/2011-us-open-venus-williams-describes-fights-with-fatigue.html?ref=tennis |title=Williams Says She Struggled With Fatigue for Years |newspaper=NY Times |date=2011 |access-date=18 February 2014 |url-status=live |archive-url=https://web.archive.org/web/20120910143445/http://www.nytimes.com/2011/09/02/sports/tennis/2011-us-open-venus-williams-describes-fights-with-fatigue.html?ref=tennis |archive-date=10 September 2012 }}
• Stephen McPhail (professional soccer player for Ireland, Leeds, and Cardiff City) was diagnosed with lymphoma and Sjögren's disease at age 29.{{cite web|date=2020-03-03|title=How Venus Williams got Stephen McPhail back on track after autoimmune disease diagnosis|url=https://www.irishexaminer.com/sport/soccer/arid-30985572.html|access-date=2020-10-03|website=Irish Examiner|language=en}}
• Halsey (singer) diagnosed with Sjogren's, Ehlers-Danlos syndrome, Mast Cell Activation Syndrome, and Postural Orthostatic Tachycardia Syndrome{{cite web | url=https://www.vanityfair.com/style/2022/05/halsey-health-scare-diagnosis-after-giving-birth-son-ender-ridley | title=Halsey Reveals They've Developed Multiple Health Problems Since Giving Birth to Son Ender | website=Vanity Fair | date=11 May 2022 }}
• Slađana Milošević (Serbian singer), died after struggling with Sjögren's disease.{{Cite web |date=2024-03-26 |title=Jutarnji list - Slađana Milošević je bolovala od opakog sindroma: 'Napada sve sustave, ni doktori ne znaju...' |url=https://www.jutarnji.hr/scena/domace-zvijezde/sladana-milosevic-je-bolovala-od-opakog-sindroma-napada-sve-sustave-ni-doktori-ne-znaju-15443552 |access-date=2024-03-27 |website=www.jutarnji.hr |language=hr-hr}}

{{Reflist}}

• Some of the original text for this article was obtained from a public domain resource at [https://www.ninds.nih.gov/health-information/disorders/sjogrens-syndrome NIH]

• {{cite journal|last1=Price|first1=EJ|last2=Rauz|first2=S|last3=Tappuni|first3=AR|last4=Sutcliffe|first4=N|last5=Hackett|first5=KL|last6=Barone|first6=F|last7=Granata|first7=G|last8=Ng|first8=WF|last9=Fisher|first9=BA|last10=Bombardieri|first10=M|last11=Astorri|first11=E|last12=Empson|first12=B|last13=Larkin|first13=G|last14=Crampton|first14=B|last15=Bowman|first15=SJ|last16=British Society for Rheumatology Standards, Guideline and Audit Working Group|title=The British Society for Rheumatology guideline for the management of adults with primary Sjögren's Syndrome.|journal=Rheumatology|date=1 October 2017|volume=56|issue=10|pages=e24–e48|doi=10.1093/rheumatology/kex166|pmid=28957550|doi-access=free}}

{{Commons category}}

• [https://www.nhs.uk/conditions/sjogrens-syndrome/ Sjögren syndrome at NHS Choices]
• [https://www.niams.nih.gov/health-topics/sjogrens-syndrome Sjögren syndrome] – US National Institute of Arthritis and Musculoskeletal and Skin Diseases
• [https://www.sjogrens.org/ US Sjögren's Foundation]

{{Medical resources

| DiseasesDB = 12155

| ICD11 = {{ICD11|4A43.2}}

| ICD10 = {{ICD10|M35.0}}

| ICD9 = {{ICD9|710.2}}

| ICDO =

| OMIM = 270150

| MedlinePlus = 000456

| eMedicineSubj = med

| eMedicineTopic = 2136

| eMedicine_mult = {{eMedicine2|emerg|537}} {{eMedicine2|derm|846}} {{eMedicine2|ped|2811}} {{eMedicine2|oph|477}} {{eMedicine2|oph|695}}

| MeshID = D012859

}}

{{Systemic connective tissue disorders}}

{{Hypersensitivity and autoimmune diseases}}

{{Oral pathology}}

{{Authority control}}

{{DEFAULTSORT:Sjogrens Syndrome}}

Category:Autoimmune diseases

Category:Connective tissue diseases

Category:Diseases named after discoverers

Category:Hepatitis C virus-associated diseases

Category:Wikipedia medicine articles ready to translate

Category:Salivary gland pathology

Category:Syndromes

Category:Syndromes of unknown causes

Category:Systemic connective tissue disorders

Category:Wikipedia neurology articles ready to translate