Have you heard of Sjogren's syndrome?

1. Sjӧgren's syndrome[1]
Introduction: It isa chronic autoimmune inflammatorydisease,mostcommoninwomenin
their50s-60s. But it can affectchildren,youngadults&men. Ina 2014 meta-analysisof
population-basedstudies,the overall incidence of SS wasestimatedatapproximately7per
100,000 people.The highestincidencerateswere reportedinstudiesfromEurope andAsia.
Sicca symptomsare more commonthan sjӧgren's,& inolderadultsare due partlyto
medicationsandpartlytoage-relatedatrophy of secretingtissueandresultantdeclinesin
tear andbasal (unstimulated) whole salivaflow rates.
Disease spectrum: It rangesfrom:
*milddisease (dryeyes/mouth, ↓ANA titers,fatigue,myalgia,mildognetive dysfunction).
*Severe disease (floridsalivaryglandenlargement,adenopathy,+ve Anti Ro& Anti La,
↓complements,cryoglobulinemia,candevelopnon-hodgkin'slymphoma).
*In a small percentage (extraglandularmanifestations,with+ve Anti Ro,+ve ANA).
Sjӧgren's syndrome isdividedinto:A primaryform:notassoiatedwithotherdiseases,&a
secondaryformassociatedwithRA & SLE.
There are fewdiffirenttermslikeKCSmarkingthe ocularfindingsanddeficiencyintear
production,Dryeye syndrome (DES) teardeficiency orexcessiveevaporation.
Many organs otherthan the exocrine glandsmaybe affectedinpatientswithSjögren’s
syndrome (SS);these include the skinandjoints;the lungs,heart,andgastrointestinaltract,
includingthe pancreasandliver;the kidneys,bladder,andgynecologicsystem;andboththe
peripheral nervoussystem(PNS) andcentral nervoussystem(CNS).
●Patients with Sjögren’s syndrome (SS) may have involvement of many types of organs
beyond the exocrine glands. Some extraglandular manifestations result from SS itself,
while others result from comorbid rheumatic or other autoimmune disease. (See
'Extraglandular organ involvement' above and 'Disease spectrum' above.)
●The major skin findings in SS include xerosis (ie, abnormal dryness); purpura,
associated with vascular or hematologic abnormalities; Raynaud phenomenon;
cutaneous vasculitis; annular erythema; and other manifestations, including eyelid
dermatitis and angular cheilitis. Although cutaneous vasculitis occurs in a significant
minority of patients, systemic necrotizing vasculitis is rare. (See 'Skin' above and
'Xerosis' above and 'Raynaud phenomenon' above and 'Cutaneous vasculitis' above
and 'Annular erythema' above and 'Other skin lesions' above and 'Vasculitis' above.)
●SS may be associated with both joint and muscle manifestations, including arthralgia
and (less often) arthritis, as well as myopathy, which is often asymptomatic. Fatigue is
one of the most common complaints in SS, but its pathogenesis is incompletely
understood. Patients with SS suffer from sleep disorders, usually due to disruption of

2. sleep patterns by a cycle of xerostomia-stimulating polydipsia with resultant polyuria.
Fibromyalgia, usually accompanied by fatigue, is also very common in SS. (See
'Musculoskeletal' above and 'Joints' above and 'Muscles' above and 'Fatigue and
fibromyalgia' above.)
●Evidence of thyroid disease, including some form of structural, hormonal, or thyroid
autoantibody abnormalities, has been found in 10 to 70 percent of patients with primary
SS in geographically diverse studies, with autoimmune thyroiditis being most common.
However, whether thyroid disease has a direct relationship to SS remains uncertain.
(See 'Thyroid disease' above.)
●The upper respiratory tract, large and small airways, and interstitium are the primary
targets of lung disease in SS. About 10 to 20 percent of SS patients have clinically
significant lung disease defined by symptoms, typically cough and dyspnea, and an
abnormal pulmonary function test or chest radiograph; a greater number of patients
have lung abnormalities detectable with additional techniques. Interstitial lung disease
can occur in SS in several forms, including non-specific interstitial pneumonitis (NSIP),
usual interstitial pneumonitis (UIP), lymphocytic interstitial pneumonitis (LIP), and
cryptogenic organizing pneumonia (COP). (See 'Lungs' above.)
●SS can cause a complex array of peripheral nervous system (PNS) and brain
abnormalities. Peripheral neuropathy affects about 10 percent of patients. Estimates of
central nervous system (CNS) involvement vary quite widely, and the nature and
frequency of CNS manifestations remain controversial. Neuropathic symptoms
frequently precede the diagnosis of SS. Depression is often associated with SS as well.
(See 'Peripheral nervous system' above and 'Central nervous system' above and
'Psychiatric disorders' above.)
●The hematologic manifestations of SS include cytopenias, especially mild anemia and
leukopenia; hypergammaglobulinemia; monoclonal gammopathies, cryoglobulinemia,
and lymphoma, and are primarily seen in patients with autoantibodies (particularly anti-
SSA/Ro or anti-SSB/La antibodies). The lifetime risk of non-Hodgkin lymphoma in SS is
approximately 5 percent. Non-Hodgkin lymphoma occurs at a mean of approximately
seven years after the diagnosis of SS. (See 'Hematologic manifestations' above.)
●Other areas may also be involved. The heart and cardiovascular system can be
affected, with increased risk of cardiovascular disease. Manifestations related to the
entire gastrointestinal tract, as well as the liver and pancreas, have been described,
including dysphagia, nausea, dyspepsia and gastritis, celiac disease, hepatic
abnormalities, and (usually subclinical) pancreatic disease, in addition to oral
involvement. Immune-mediated renal disease, including interstitial nephritis, can occur
in patients with SS; as may bladder dysfunction, with symptoms of interstitial nephritis
and gynecologic symptoms, including vulvovaginal dryness, pruritus, and dyspareunia.
Diagnostic criteria:

3. ACR classificationcriteria : adoptedin2012, thisclassificationcriteriahave been
developedthroughaconsensusapproachbythe Sjӧgren’sInternational
CollaborativeClinical Alliance (SICCA) investigators.These criteriado not
distinguishbetweenprimaryandsecondaryformsof SS.
The proposedcase definitionforSSrequiresatleasttwoof the followingthree
findings:
●Positive serumanti-Ro/SSA and/oranti-La/SSBantibodytestingORa positive
rheumatoidfactorandan antinuclearantibody(ANA) titer≥1:320
●Ocularstainingscore ≥3 (assumingthe individual isnotconcurrentlyusingdaily
eye drops)
●Presence of focal lymphocyticsialadenitiswithafocusscore ≥1 focus/4 mm2
in
labial salivaryglandbiopsysamples
The ACR criteriadifferfromthe well-establishedAECGcriteriainnotincluding
criteriabaseduponsymptomsof glandularmanifestations(ie,ocularandoral
dryness).
Evaluation of patients:
History taking: these questionsare from the AECG criteria for SS:
For ocularsymptoms:“sensationof sand orgravel in eye”,“dailypersistenttroublesomeeye
dryness>3 months”,“tear substitutes>3timesa day”.
For oral symptoms:“Dry mouth> 3 months”, “havingto drinkliquidsto aidswallowingdry
food”,“Recurrentlyorpersistentswollensalivaryglands asanadult”.
*Physical examinationhastobe thorough,lookingforsalivary/lacrimal glandenlargement,
dental caries,oral candidiasis,absentsalivarypoolingunderthe tongue.
Tests for dry eye:
- Schirmertest: Reflex tearproductionismeasuredusingthe Schirmertest.A foldedtest
stripof sterile filterpaperisplacedoverthe marginof eachlowereyelidatthe junctionof
the middle andlateral thirds.The extentof wettingismeasuredoverfive minuteswiththe
patient’seyesgentlyclosed.Wettingof < 5 mmis indicative of aqueousteardeficiencyand
isa classificationcriterionforSjögren’ssyndrome (SS).The findingsare similarinbotheyes.
- Ocular surface staining:Damage to conjunctival andcorneal epithelial cellsmaybe
assessedwithvital dyeswhichstainareasof devitalizedtissue.Since the use of Rose Bengal
dye ispainful inpatientswithdryeyes,itisbeingsupplantedbythatof fluorescein (tostain
the cornea) and lissamine green(tostainthe conjunctiva).The eyesare observedwithaslit
lamp.

4. - Tear break-up time:The TBUT measurestearstability.Itisperformedbystainingthe tear
filmwithone dropof fluorescein dye andmeasuringthe time insecondsforadry spot,or
disruptioninthe tearfilm,todevelop.Visualizationof the tearfilmwithslit-lamp
magnificationandcobaltblue lightisrequired.A TBUTof ≤10 secondsisabnormal and
indicative of adeficiencyorabnormal qualityof the outermostmucuslayerof the tearfilm.
Testsfor quantifyingsalivary hypofunction:
- Salivary gland scintigraphy:also termedtechnetiumexcretionradionuclide scanning,
providesadynamicpicture of the functionof all majorsalivaryglands[66].The findingof
verylowuptake of the radionuclide isrelativelyinsensitivebut highlyspecificforSS.
Approximatelyone-thirdof patientswithSShave positivetests
- Whole sialometry:It isthe measurementof the rate of salivaproduction.The
unstimulatedwholesalivaryflowrate isa relativelysimpletestthatassessesbasal saliva
production,primarilyfromthe sublingual andsubmandibularglands,andavoidsthe need
for special equipmentorimagingagents.Itdeclineswithage andhasa negative correlation
withthe extentof dental caries.The patientisaskedtoexpectorate once andthentocollect
all salivaintoa pre-weighedcontainer.After5to 15 minutes,the collectionvial isreweighed
and the volume of salivaiscalculatedusingthe specificgravityforwater(1 gram/mL).A
collectionof ≤0.1 mL/minduringthistime isconsideredtobe apositive test.
Whole sialometry withstimulationof salivasecretion, bychewingorsialogogues(suchas
citricacid or pilocarpine), predominantlymeasurestimulatedparotidsalivaproduction.
Saxontest:Salivaquantitationusingapre-weighedspongeisone methodof whole
stimulatedsialometry.The patientchewsapre-weighedgauze sponge fortwominutes
withoutswallowing.The difference inthe weightof the sponge before andafterchewing
represents the amountof salivaproduced .Data fromnormal subjectssuggestthatan
accumulationof lessthan2.75 grams of salivaon the sponge overa two-minuteperiod
constitutesapositive test.
Salivary gland imaging:
Magneticresonance imagingof the parotid glands: InSS it ischaracterizedby
inhomogeneityof the parenchymaonbothT1- and T2-weightedsequences.There
istypicallyanodular“honeycomb”or“salt and pepper”pattern thatisthoughtto
arise fromfatty infiltration,fibrosis,ductal dilatation,andlymphoidinfiltrationof
parotidlobules.MRIresultscorrelate well with thoseof salivaryglandbiopsy.
Gadolinium-enhancedMRhelpsperformingsialographyonsalivaryglands
noninvasively.

5. Salivary gland ultrasonography: the diseasedglandinSStypicallyshowsmultiple
hypoechoicareaswithconvex borders.Hyperechoiclinearbands,cysts,andcalcifications
may be evidentinmore advanceddisease.SalivaryglandUShasdiagnosticvalue inSS
comparable withthatof scintigraphyorsalivaryglandbiopsy
Other imagingtechniques
●Computedtomography of the parotids: Diffuse punctate calcification,bestseen
on CT, isa highlyspecificfindingforSS
●Parotid gland contrast sialography: performedbyretrograde cannulationof the major
salivaryglandducts,followedbyinstillationof anoil-basedcontrastmaterial.Althoughthis
methodgivesexcellentvisualizationof the ducts,itislimitedbythe riskof rupturingthe
duct & nowsubstitutedbyMR sialography.
Serologicand other laboratory testing:
Routine laboratorytesting(complete bloodcount,chemistrypanel,urinalysis,and
erythrocyte sedimentationrate [ESR]) mayreveal findingssupportiveof SS,
includingaleukopenia, ↑ globulins,and ↑ ESR(usuallyareflectionof the
elevatedglobulins).The urine mayreveal signsof glomerulonephritis(redcell
casts, proteinuria)orinterstitial nephritis/renaltubularacidosis(mildproteinuria,
hyposthenuria,urine pH≥7 in the face of a metabolicacidosis).
It isrecommendtotestfor antinuclearantibodies(ANA)byimmunofluorescence
stainingassay,anti-Ro/SSAandanti-La/SSBantibodies,andrheumatoidfactor.The
ANA testshouldnotbe usedas a screeningtestforSS,since some patientsmay
have anti-Ro/SSA and/oranti-La/SSBantibodiesdespite anegative
immunofluorescencestainingassayforANA.
Antibodiesto Ro/SSA and La/SSB: PatientswithprimarySSoftenpossessantibodiestothe
Ro/SSA or La/SSBantigens,andmanypatientspossessboth.The frequencyof anti-Ro/SSA
and/oranti-La/SSBantibodieshasvariedbetweenstudies,butgenerally60to 80 percentof
patientswithprimarySSexhibitone orbothof these autoantibodies.
Labial Salivary gland biopsy:It can serve as an importantdiagnostictool in
patientswithsuspectedSS.Indicationsinclinical practice include:
● Confirmationof asuspecteddiagnosisof SS,particularlyinpatientswithout
otherevidence of autoimmunity
● Exclusionof otherconditionsthatcancause salivaryhypofunctionandbilateral
glandenlargement

6. The keyhistologicfeature isafocal collectionorcollectionsof tightlyaggregated
lymphocytes,termedlymphocyticfoci,whichare typicallyperiductal.Thishistologicpattern
isknownas focal lymphocyticsialadenitis.
Diffirential diagnosis:
- InfectionslikeHIV,HCV,HTCLV
- Sarcoidosis(if suspected,obtainplainCXR)
- Age relatedsiccasymptoms
- IgG4 relateddisease(autoinflammatorydisease)
- Anticholinergicdrugs, TCA.
Management:
- Artificial tears
- Artificial salivasupstitutes
- Maintaingoodhydration
- Routine 6 monthlyvisitstodentist
- Pilocarpines&gum can increase salivaproduction
In more aggressive or severe disease:
- HXQ (hydroxychloroquine) >jointinvolvement
- Rituximab>huge swollensalivaryglands
- Systemicglucocorticoids>jointinvolvement
References:
[1] UpToDate website
http://www.uptodate.com/home