Damage and/or cell death due to viral infection or other causes may provide triggering antigens to Toll-like receptors in or on dendritic or epithelial cells, which, by recognizing pathogen-associated patterns, are activated and begin producing cytokines, chemokines, and adhesion molecules. As T and B lymphocytes migrate into the gland, they themselves become activated by dendritic and epithelial cells, thereafter acting as antigen-presenting cells. Expressed antigens include SSA/Ro, SSB/La, alpha-fodrin and beta-fodrin, and cholinergic muscarinic receptors. Dendritic cell triggering by immune complexes formed from SSA ̶ anti-SSA (or other immune complexes) may propagate the ongoing innate and acquired immune activation.
Sex hormones may influence the immunologic manifestations of primary Sjögren syndrome, because the disease is much more common in women than in men. The prevalence of serologic markers tends to be lower in male patients than in female patients. Although the role of sex hormones (eg, estrogens, androgens) in the pathogenesis of primary Sjögren syndrome remains unknown, adrenal and gonadal steroid hormone deficiency probably affects immune function.
Venus Williams, is an American professional tennisplayer who is a former World No. 1.She is 32-year-old,African-American female. Was admitted to your clinicsuffering severe xerophthalmia (dry eyes), xerostomia(dry mouth), xeroderma and parotid gland enlargement .The erythrocyte sedimentation rate (ESR) was 105 mm/h(N:0-10 mm/h).She complained from severe fatigueepisodes while training and playing. Some tests wereperformed and the results were as shown below: Schirmers test : <4 mm wetting of the paper after 5 minutes . N: ≥15-10 mm after 5 minutes Positive salivary gland biopsy findings. Positive anti–SSA & anti–SSB antibodies results. unstimulated salivary flow < 1.5mL in 15min N: 0.3 - 0.4 ml/min (5.25 ml in 15 min)
Venus Williams is suffering from: Sjögrens Syndrome.OverviewSjögrens syndrome(S.S) is a systemic, chronic,autoimmune, inflammatory disorder. Characterized bylymphocytic infiltrates in exocrine organs. Most individualswith Sjögren syndrome present with sicca symptoms.In addition, numerous extraglandular features maydevelop.Primary Sjögren syndrome occurs in the absence ofanother underlying rheumatic disorder, whereas SecondarySjögren syndrome is associated with another underlyingrheumatic disease, such as (SLE), rheumatoid arthritis (RA),
Etiology:The etiology of Sjögren syndrome is not well understood.Autoimmune diseaseongoing interaction between the innate and acquired immune systems.There is presence of activated salivary gland epithelial cells expressingmajor histocompatibility complex (MHC) class II molecules.Association with the human leukocyte antigen(HLA)Some evidence indicates that the true association of Sjögren syndromemay be with HLA-DQA1.According to Israeli research ,HLA-DR5 is associated with S.S in Israelipersons.Possible disease triggersViruses are viable candidates as environmental triggers, uncertain.Epstein-Barr virus (EBV), HTLV-1, human herpesvirus 6 (HHV-6), HIV,hepatitis C virus (HCV), and cytomegalovirus (CMV) may have a role.Glandular pathologyNew studies (Jan-2003) : role of apoptotic mechanisms in the pathogenesisof primary Sjögren syndrome. A defect in Fas-mediated apoptosis, which isnecessary for down-regulation of the immune response, can result in a
EpidemiologyIN USA: Second most common rheumatologic disorder, behindSLE. Sjögren syndrome affects 0.1-4% of the population.Between different ethnic groups , the disease occursworldwide with similar prevalence.The female-to-male ratio of Sjögrens syndrome is 9:1.-The Journal of Clinical Endocrinology & Metabolism Vol. 94,No. 6 2044-2051(2009)- Dehydroepiandrosterone (DHEA)Role.-2011 -Charles E. Schmidt College of Medicine, Florida-Atlantic University.Sjögren syndrome can affect individuals of any age but is
PrognosisSjögren syndrome carries a generally goodprognosis.Morbidity associated with Sjögren syndrome ismainly associated with the gradually decreasedfunction of exocrine organs.Patients with primary Sjögren syndrome have anormal life expectancy.Children born to mothers with antibodies againstSSA/Ro are at an increased risk of neonatal lupusand congenital heart block.
PresentationThe first symptoms in primary Sjögren syndrome can beeasily overlooked and overlapped.Xerophthalmia (dry eyes) and xerostomia (dry mouth) arethe main clinical presentations in adults. Bilateral parotidswelling is the most common sign of onset in children.Extraglandular involvement in Sjögren syndrome falls into 2general categories:Periepithelial infiltrative processes include interstitialnephritis, liver involvement, and bronchiolitis and generallyfollow a benign course.Extraepithelial extraglandular involvement in Sjögrensyndrome is related to B-cell hyperreactivity,hypergammaglobulinemia, and immune complex formationand includes palpable purpura, glomerulonephritis, and
Sicca symptoms (dry eyes and dry mouth and dry vagiFatigue.Parotitis.Cutaneous symptomsPulmonary symptoms(xerotrachea),which can manifest as a dry cough.Gastrointestinal symptoms.Cardiac symptoms.Renal disorders.A history of recurrent miscarriages or stillbirthsNeurologic symptoms.(see neurology corner).
Diagnosis of primary Sjögren syndrome requires 4out of 6 of the below criteria:Ocular symptoms - Dry eyes for more than 3months, foreign-body sensation, use of tearsubstitutes more than 3 times daily.Oral symptoms - Feeling of dry mouth, recurrentlyswollen salivary glands, frequent use of liquids to aidswallowing.Ocular signs – Schirmer’s test performed (< 5 mmin 5 min).Oral signs - Abnormal salivary scintigraphyfindings, abnormal parotid sialography findings,abnormal sialometry findings (unstimulated salivaryflow < 1.5mL in 15min) .
WorkupNo single test is sufficiently sensitive or specific inthe diagnosis of Sjögren syndrome.Laboratory test results may indicate the following:•Elevated erythrocyte sedimentation rate (ESR)•Anemia•Hypergammaglobulinemia•Presence of antinuclear antibodies, especially anti-Roand anti-La•Presence of anti–alpha-fodrin antibody (reliablediagnostic marker of juvenile Sjögren syndrome)•Creatinine clearance may be diminished in up to 50% ofpatientsSchirmer test.Serum electrophoresis.Sialography and Scintigraph.
Differential diagnosis: ^ ^ Parkinson disease.Sarcoidosis Bell’s palsy.Graft versus host disease AmyloidosisHIV infection SarcoidosisHTLV-1 infection LymphomaHCV infection Viral infection (eg, mumps,Keratoconjunctivitis sicca Epstein-Barr virus,Anxiety and depression cytomegalovirus, coxsackievirusViral infections (eg, mumps) A, influenza)Complications from contact lenses DILS associated with HIVDehydration diseaseHypervitaminosis A Granulomatous diseasesNeurotropic keratitis (sarcoidosis, tuberculosis,Mucous membrane pemphigoid leprosy)Environmental irritants HyperlipoproteinemiaMouth breathing Hepatic cirrhosisChronic blepharitis Hepatitis CChronic conjunctivitis BulimiaRosacea Recurrent parotiditis ofTherapeutic radiation or surgery to the head and neck childhoodAge Chronic pancreatitisAlzheimer disease
Treatment:No curative agents for Sjögren syndrome exist. The treatment of the disorder is essentially symptomatic. In secondary Sjögren syndrome, treatment is based onthe accompanying disease and its clinical features.Skin and vaginal drynessPatients should use skin creams, such as Eucerin, or skinlotions, such as Lubriderm.Arthralgias and arthritisAcetaminophen or nonsteroidal anti-inflammatory drugs(NSAIDs).
Dry Eyes:•Artificial tears should be applied liberally.•Topical steroids.•Cyclosporine.•Nutritional supplements.Dry mouth:•Patients with dry mouth can liberally drink sips ofwater and take bottled water with them on trips.Additional treatment considerations:•In patients with major organ involvement, such aslymphocytic interstitial lung disease, considertherapy with steroids and immunosuppressiveagents, such as cyclophosphamide.
Surgical TherapyOcclusion of the lacrimal puncta canbe corrected surgically. Electrocauteryand other techniques can be used forpermanent punctal occlusion.
S.S Could be associated Brain and spinal cord: with Pachymeningit Central & peripheral manifestations : is and hypophysitis Myelitis. DEVIC’S Peripheral syndrome. manifestations: Autonomic neuropathy Trigeminal neuralgia and glossopharyng eal neuralgia Mononeuritis multiplex.Designed by :
Pachymeningitis /pachy·men·in·gi·tis/ (-men″in-ji´tis) inflammationof the dura mater.Pachymeningitis Normal .Case.
Hypophysitis refers to an inflammation of the pituitary gland.Hypophysitis is rare and not fully understood.
Myelitis involves the infection or the inflammation of white matter orgray matter of spinal cord.
Devics syndrome, is an autoimmune, inflammatory disorderin which a persons own immune system attacks the opticnerves and spinal cord.
S.S Could be associated Brain and spinal cord: with Pachymeningit Central & peripheral manifestations : is and hypophysitis Myelitis. DEVIC’SPeripheral syndromemanifestations:Autonomicneuropathy.Suicidedisease.Glossopharyngeal neuralgia.Mononeuritismultiplex.Designed by :
Mononeuritis multiplex is a painful, asymmetrical, asynchronous sensoryand motor peripheral neuropathy involving isolated damage to at least 2separate nerve areas.
41. A 57-year-old woman with a historyof hypertension,arthritis, Xerophthalmia, and xerostomia. was referred to arheumatologist for evaluation.A mini-chem panel shows no electrolyteabnormalities. Her erythrocytesedimentation rate (ESR) is elevated,and an antinuclear antibody test (ANA)is positive. Further antibody studies areperformed, and the results are shownbelow.Anti-histones high titer.Anti-SSA detectedAnti-SSB detectedAnti-Smith not detectedAnti-centromere not detectedAnti-RNP detected.Which of the following diseases issuggested by these results?(A) CREST syndrome(B) Diffuse form of scleroderma(C) Drug-induced lupus(D) Sjögren syndrome