Sialadenitis/Parotitis/Sjogren’sSialadenitis/Parotitis/Sjogren’s

Vincent Steniger, D.M.D

4-17-08

OutlineOutline

Case presentationSialadentitis/ Overall Salivary Gland

InfectionsParotitis Sjogren’s Syndrome

Chief ComplaintChief Complaint 53 y/o white, male patient presents with a chief complaint as

follows:– “Would like my broken front teeth fixed”– “Would like to check on my swollen glands”

Interpretation of Chief Complaint:– #7 and #8 Fractured– Presents with right Parotid Gland swelling, negative

pain, tenderness

History of Present IllnessHistory of Present Illness Current Medical

Conditions:– Diabetes Type II (1995)– Asthma (1994)– Hx of Submandibular

Salivary Stones and Swelling and resection of SM glands in 1987

– Hx of both R & L Parotid Swelling, sometimes with Pain

– GERD (2007)

Current Medications:– Glucotrol (5mg/day) (Stimulates

pancreas to secrete insulin. Sulfonoylurea Blocks K+ in Islet Cells leading to greater increase in Insulin Secretion)

– Prevacid (H Pump Inhibitor)

– Multivitamin– Zyrtec

Antihistamine – Mucinex

Expectorant draws water from the lungs aiding in getting rid of phlegm

– Oasis Mouth Spray Essential oils, Glycerol

Past Medical HxPast Medical Hx (SHH) (SHH) HEENT

– Pt wears glasses– Seasonal Allergies

CV System:– Pt denies Prosthetic Valve,

Congenital Heart Disease, RF, Endocarditis

Respiratory: – Asthma

Renal: – Hx of Proteinurea

Urinary/Reproductive: Ø

Endocrine: – Diabetes Type II – SM Glands Removed (1987)– Hx of R and L Parotid Swelling

and Pain possible Sjogren’s– Hx of minor gland above the L.

eye removed (1999) (Lacrimal) Gastro-intestinal/Hepatic:

– GERD– Gall Bladder removal (1984)

Dermatological: Ø Infectious:

– Denies HIV/AIDS, Hep A, B, C, TB

Autoimmune: Ø Neoplastic: Ø

EOE/ IOEEOE/ IOE Very Swollen Right Parotid for

which the pt says “this is actually normal, it gets much bigger than this”

No Skin Lesions Lips were of healthy color Left Parotid Gland WNL Scar can be seen across the neck

from wear the SM glands were resected

Scar above left eye where gland resected

+Sialomegally -Lymphadenopathy -Thyromegally

Heavily Restored Dentition Multiple Amalgam Fillings Missing #’s 1-5, 16, 17, 19,

20, 29, 31, 32 A few areas of

staining/possible caries Mild Gingivitis/

Recession/Moderate Periodontitis (Some Mobility)

Noticeably dry oral cavity Class I Occlusion

SialadentitisSialadentitis

What is Sialadentitis?– Simply inflammation of the salivary glands– Can be due to a number of factors including:

Mumps infectionCoxacki VirusParainfluenzaSystemic Disease

Sialadentitis: EtiologySialadentitis: Etiology May be infectious:

– May be caused by bacterial or viral infections May be non-infectious:

– May be caused by systemic disease such as Sjogren’s or Sarcoidosis or even by radiation therapy

May be Post-Surgical:– Called “Surgical Mumps”– Pt kept without fluids and given atropine causes xerostomia

predisposing to inflammation May be Pharmacological:

– Drugs causing xerostomia May be architectural:

– Block of the salivary gland due to a stone

ParotitisParotitis Definition:

– Inflammation of the Parotid Gland May be infectious or non-infectious Common Causes:

– Mumps– Sjogren’s Syndrome– Bacterial infection of parotid gland usually Staph.

aureus– Blocked salivary duct – Stone in salivary duct

Parotitis: SymptomsParotitis: Symptoms Pain/ Tenderness of the Parotid Glands Enlargement of the Parotid Glands Infectious parotitis

– Acute bacterial parotitis: The patient reports progressive painful swelling of the gland; chewing aggravates the pain.

– Acute viral parotitis (mumps): Pain and swelling of the gland last 5-9 days. Moderate malaise, anorexia, and fever occur. Bilateral involvement is present in most instances.

– HIV parotitis: Nonpainful swelling of the gland occurs; otherwise, patient is asymptomatic.

Parotitis in tuberculosis: Chronic nontender swelling of one parotid gland occurs, or a lump is noted within the gland. Symptoms of tuberculosis are found in some cases.

Sjogren’s Syndrome: Recurrent or chronic swelling of one or both parotid glands with no apparent cause is noted. It is frequently associated with autoimmune disease. Discomfort is modest in most cases and is related to dry mouth and eyes.

Recurrent parotitis of childhood: Repetitious episodes of unilateral or bilateral mumps-like episodes in a young child are indicative.

Sarcoidosis: Chronic nontender swelling of parotid gland occurs

Overall Treatment for Parotitis Overall Treatment for Parotitis Acute:

– Antibiotics– Rehydration stimulating salivary flow– Possible IND

Chronic:– Eliminate causative agent:

Get rid of salivary stone/ other blockage– Warm Compresses– Sialogogues– Possible surgical resection – Ligation of the duct in hopes of atrophy

MumpsMumps

Mumps: (Viral Parotitis)Mumps: (Viral Parotitis)

Acute sialadenitis caused by RNA virus – Paramyxovirus

Other viruses causing salivary gland infection:

– Cytomegalovirus– Coxsackieviruses– Echovirus

Mumps: Clinical FeaturesMumps: Clinical Features Transmitted via airborne droplet Mainly effects the parotid gland Mainly effects children between the ages of 5-18 Has a 2-3 week incubation period Clinically:

– Will see rapid swelling of the parotids bilaterally– Acute pain when salivating

Clinical Features- continuedClinical Features- continued

When looking at the patient:– The ear lobe is elevated due to glandular enlargement

There may be a purulent discharge from the parotid duct but it is clear and unremarkable

Blood Work:– As the acini become infected the salivary amylase leaks

into the interstitium and is absorbed in the blood stream raising the serum amylase levels

Mumps: HistopathologyMumps: Histopathology

There is infiltration with plasma cells and the lymphocytes

The ductal lumens contain desquamated cell debris and leukocytes

Mumps: TreatmentMumps: TreatmentThere no effective antiviral therapy

available for the treatment of mumps.Analgesics and antipyretics are given to

control pain and feverLiquid diet with vitamins Bed rest

Sjogren’s SyndromeSjogren’s Syndrome

Sjogren’s SyndromeSjogren’s Syndrome

It is a group of autoimmune conditions with a marked predilection for woman, it has an intense T lymphocyte – mediated autoimmune process in salivary and the lacrimal glands as on of its most prominent component

Sjogren’s syndrome exhibits T cells infiltration and replaces the glandular parenchyma

Sjogren’s SyndromeSjogren’s SyndromeSjogren’s Syndrome:

– objective evidence of keratoconjunctivitis sicca – characteristic pathologic features of the salivary

glands– 2 out of 3 of:

recurrent chronic idiopathic salivary gland swelling unexplained xerostomia connective tissue disease

Sjogren’s Syndrome: Who is effected?Sjogren’s Syndrome: Who is effected?

Sjogren’s Syndrome can be Primary or Secondary:– Primary the syndrome is second to nothing

Only effects the salivary glands and the lacrimal glands

– Secondary Sjogren’s secondary to something like Rheumatoid Arthritis, SLE or Scleroderma

0.5-1% of the population is effected Age ranges for Sjogren’s 20-40 years 9:1 women effected more

Sjogren's Syndrome: Age of OnsetSjogren's Syndrome: Age of Onset The frequency distributions of ages at onset of symptoms & at diagnosis of primary Sjogren's syndrome

05

1015202530354045

1-10 11-2021-3031-4041-5051-6061-7071-80

81-90AGE

% O

F PA

TIEN

TS At diagnosisAt diagnosisOnset Onset

Sjogren’s Syndrome: ClinicallySjogren’s Syndrome: Clinically Subjective and Objective Findings: Subjective:

– Xerostomia– Salivary Gland Enlargement

Objective:– Stomatitis– Oral Ulcers– Cracked, “crocodile skin” tongue – Carious Teeth– Parotid Gland Enlargement– Certain Tests can be done

“ “Crocodile Skin” Tongue, Carious TeethCrocodile Skin” Tongue, Carious Teeth

Tests and Studies: ScintigraphyTests and Studies: Scintigraphy Scintigraphy (Nuclear Medicine) administer radioactive substance

in order to show the physiology and state of the biological process:

Scintigraphy diagnosis Normal Moderate

involvementMarked

involvementDegree of xerostomia None Mild Severe

Salivary flow rate (ml/5-min/gland)

1.60 0.42 0.00

Scintigraphy: ContinuedScintigraphy: Continued

With Sjogren’s Syndrome there will be delayed uptake and concentration of marker as well as delayed excretion

Tests and Studies: Schirmer’s Test Tests and Studies: Schirmer’s Test A test of whether the eye has enough tears to keep moist Procedure:

– Piece of filter paper inserted for several minutes (usually 5) and moisture recorded

<5 ml in 5 minutes is characteristic of Sjogren’s Syndrome

Tests and Studies: SerologyTests and Studies: Serology

Autoantibodies % positiveRheumatoid factors (Igs) 80

Cryoglobulins (type II)

30

Ro/SSA 60La/SSB 30a-fodrin 95

Tests and Studies: Salivary Gland BiopsyTests and Studies: Salivary Gland BiopsyA lip biopsy, if positive for Sjogren’s will

show lymphocytes clusters and glandular destruction due to inflammation

Tests and Studies: Salivary Flow RateTests and Studies: Salivary Flow Rate

Stimulated Unstimulated

Sjogren’s Syndrome: Exclusion CriteriaSjogren’s Syndrome: Exclusion Criteria Prior head and neck irradiation Pre-existing lymphoma Acquired immunodeficiency disease (AIDS) Hepatitis C infection Sarcoidosis Graft‑versus‑host disease Sialoadenosis Drugs (neuroleptic, anti‑depressant, anti‑hypertensive,

parasympatholytic)

Sjogren’s Syndrome: Differential DiagnosisSjogren’s Syndrome: Differential Diagnosis

HIV, HCV infection

Sarcoidosis

Amyloidosis

Lipoproteinemia

Chronic graft-versus-host disease

Lymphoproliferative disorders

Sjogren's Syndrome Sjogren's Syndrome Algorithm for the diagnosisAlgorithm for the diagnosis

If positive

Sjogren's Syndrome

Dry mouthDry eyes

Salivary gland enlargement

Raynaud’s phenomenon PurpuraRenal tubular acidosis

or or

Eye & salivary gland tests Serology

If any positive

Sjogren’s Syndrome: PathophysiologySjogren’s Syndrome: Pathophysiology Insult may start with a bacterial or viral infection. The

peptides and antigens associated with the bacterial or viral infection along with autoantigens (self being recognized as foreign) are associated with HLA II complex that gets expressed on CD4+ T Cells. Once the HLA is expressed, there is release of cytokines and further T Cell activation

After the initial attack of the CD4+ T Cells, B cells enter the gland and make autoantibodies, including, in many cases Anti-SS-A (Ro) and Anti-SS-B (La) (only Sjogren’s Syndrome) and in some cases Rheumatoid Factor. Via autoimmunity, and antigens being expressed to CD4+ T cells, the acini of the gland are destroyed

Pathophysiology: ContinuedPathophysiology: Continued Multifactorial disease SS is sometimes called autoimmune epithelitis in which there

is apoptosis of epithelial cells leading to degradation products and leading to antinuclear autoantigens to the immune system

Molecules within the TNF family play a big role in the polyclonal activation of B Cells. This, in turn leads to autoantibodies

There is known inhibition of healthy glands and/or the muscarinic receptors (via antibodies) and also abnormal function of aquaporins leading to poor function of remaining healthy glandular structure

There is prolonged/permanent activation of autoreactive B cells favoring oncogenic activity and possible development of B Lymphoma

Parotitis/Sjogren’s: HistologyParotitis/Sjogren’s: Histology Acute Parotitis:

– See inflammatory infiltrate (neutrophils) around the ductal system and acini

– Destruction of epithelial tissues Chronic Parotitis:

– Inflammatory infiltrate in the parenchyma of the gland (Plasma Cells and Lymphocytes)

The basic features are massive lymphoid infiltration with atrophy of the acini, proliferation of the cells of the small ducts that leads to narrowing of the lumen, and finally, obliteration of the gland

NormalNormal

Pathological

Sjogren’s Syndrome: Systemic ManifestationsSjogren’s Syndrome: Systemic Manifestations

Systemic manifestations Frequency (%)Arthralgia/arthritis 60Raynaud’s phenomenon 30Purpura/Vasculitis 15 (1)Lung involvement(increased liver enzymes)

10 (25)

Kidney involvement(Interstitial Nephritis/Glomerulonephritis)

8 (25)

Liver involvement 5Muscle involvement 1

Skopouli et al., Semin Arthritis Rheum. 2000, 29:296

“Evaluation of sialometry and minor salivary gland biopsy in classification of Sjögren's Syndrome patients”

Revista Brasileira de Otorrinolaringologia vol.71 no.3  São Paulo May/June 2005 Liquidato et alCohort Study

There is no gold standard for the diagnosis of Sjogren’s Syndrome

In the past, biopsy and salivary flow rates were used Minor Salivary Gland biopsy is the most accurate

diagnosis means but is not used as a criteria for the diagnosis of Sjogren’s, rather it is helps confirm the diagnosis when there is a blood test confirming presence of Anti-SSA or Anti-SS-B

Study wants to know if there is a less invasive way to have an accurate diagnosis of Sjogren’s Syndrome

Why Do the Study?

Purpose of the StudyPurpose of the Study The present study aimed at assessing the role of minor

salivary gland biopsy and sialometry, either isolated or associated, as methods used to classify Sjögren's Syndrome based on the criteria defined by the European Community Study Group on Diagnostic Criteria for Sjögren's Syndrome

Materials and Methods: SubjectsMaterials and Methods: Subjects – 72 patients coming to the Department of Otorhinolaryngology, in

Sao Paulo Brazil from 1997 to 2003– Based on a criterion showed, they were submitted into the

investigation for diagnosis– Patients split into 2 groups those with the diagnosis of

Sjogren’s already, and those without the diagnosis of Sjogren’s– 26 pts with Sjogren’s and 46 pts not yet dx with Sjogren’s– Those with Sjogren’s were broken up into Primary or Secondary

Sjogren’s– To classify patients with primary Sjögren's Syndrome we

required the presence of 4 out of 6 items and item 4 (histopathology) or 6 (auto-antibodies) had necessarily to be present. As to classification of patients with secondary Sjögren's Syndrome, it required the presence of item 1 or item 2 plus 2 other items numbered 3, 4 and 5

Materials and Methods: Materials and Methods: Methods:Methods:

Non-stimulated sialometry:– Used 2 pre-weighed cotton balls– Subjects swallowed all saliva, then cotton balls put on the floor of

the mouth for 2 minutes, then weighed again– Anything 0.1ml/minute considered abnormal

Minor Salivary Gland Biopsy:– Horizontal incision parallel to the vermillion border of the lower

lip– Took about 4-6 minor salivary glands– Histopathological findings were graded as follows: normal gland;

mild inflammatory process; moderate inflammatory process; severe inflammatory process, and presence of inflammatory foci

A Review…A Review… sensitivity = probability of a positive test among patients with disease specificity = probability of a negative test among patients without

disease positive predictive value = the proportion of patients with positive

test results who are correctly diagnosed. It is considered the physician's gold standard, as it reflects the probability that a positive test reflects the underlying condition being tested for

negative predictive value = the proportion of patients with negative test results who are correctly diagnosed

Results:Results: As to the number of inflammatory foci found on biopsy:

– Those with Primary Sjogren’s had more than those with Secondary Sjogren’s who had more than those with no diagnosis of Sjogren’s

Current Article:– Biopsy Sensitivity of 72%, Specificity of 84%

Positive Predictive Value of 75% Negative Predictive Value of 82% Meaning 84% of the time, those with SS will have a positive biopsy Meaning 72% of the time, those without SS will have a negative biopsy Meaning 75% of the time, those with a positive biopsy will have SS dx

correctly Meaning 82% of the time, those with a negative biopsy will not have SS

– Sialometry Sensitivity of 62%, Specificity of 52% Negative Predictive Value of 71%

– Biopsy Accuracy 79%– Both Biopsy + and Sialometry + Specificity of 95%, PPV of 86%

ConclusionConclusion Sialometry higher sensitivity and specificity in Primary vs

Secondary group– There is higher likelihood of the subject not having Sjögren's

Syndrome when sialometry is negative Biopsy higher sensitivity and specificity in Primary vs Secondary

group– A subject would have 75% likelihood of having Sjögren's

syndrome when biopsy was positive and 81.6% likelihood of not having Sjögren's syndrome when biopsy was negative

Case StudyCase Study

Recurrent Parotitis as a First Manifestation of Adult Primary Sjogren’s Syndrome

Sugimoto et alThe Japenese Society of Internal Medicine

January 17th, 2006Case Report

Case SubjectCase Subject 38 year-old Japanese women with 3 year history

of bilateral parotitis Denied dry eyes, dry mouth, trouble swallowing,

arthralgias Lab Tests:

– Rheumatoid Factor– Positive for Anti-SS-A/Ro Antibodies (found in 45% of

Primary Sjogren’s Patients)– No Anti-SS-B/La Antibodies (found in 15% of Primary

Sjogren’s Patients)

Salivary Function:– Unstimulated Salivary Flow 0.2ml/10 min– Stimulated Salivary Flow 2.0ml/10 min

Labial biopsy of minor salivary glands revealed lymphocyte infiltration and glandular and ductal atrophy

Diagnosed with Primary Sjogren’s Syndrome

Salivary Function and Biopsy

ConclusionConclusion Recurrent Suppurative Parotitis is a common first manifestation in

children and adolescents Recurrent Parotitis being the first manifestation is rare, but can

happen Treatment for Recurrent Parotitis:

– Because of stasis of saliva within the gland, there is usually bacterial infection, thus antibiotics are common some literature promotes Antibiotic Prophylaxis to prevent this as some patients can feel prodromal symptoms before inflammation/infection of the gland

Point of the article:– Consider Sjogren’s Syndrome within the differential as the

underlying cause of Recurrent Parotitis, even in adults

Case Patient:Case Patient: Has had recurrent submandibular infection, stones, swelling to which the

glands were removed Has had his right lacrimal gland removed because of swelling Has now had recurrent bouts of Parotitis, some suppurative Has constant xerostomia for which Oasis mouth spray is used HAS NEVER BEEN WORKED UP FOR SJOGREN’S

– PCP NEVER MENTIONED IT– ENT DIDN’T MENTION IT– PLASTIC SURGEON BROUGHT IT UP

To Do For The Patient:To Do For The Patient:

Refer to Sjogren’s specialistBlood tests for Anti-SS-A(Ro), Anti-SS-

B(La) and Rheumatoid FactorStimulated, Unstimulated Salivary FlowMinor Salivary Gland BiopsyConfirm Dx of Sjogren’s Syndrome

Sjogren’s Syndrome: Sjogren’s Syndrome: TreatmentTreatment

Glandular Stimulation/Replacement To Treat Xerostomia:

– Salivary Substitutes– Dx and treatment of candidiasis – Meticulous oral hygeine for prevention of caries

To Treat Xerophthalmia:– Stimulation for tears:

Cyclosporin A Pilocarpine Cimeviline

Treatment: ContinuedTreatment: Continued Treatment for Salivary Gland Enlargement:

– Local moist heat– Antibiotic Therapy– NSAIDs– Rule out a Lymphoma

Treatment for Peripheral Symptoms:– Methotrexate– Cyclosporin A– Infliximab– Hydroxychloroquine– Corticosteroids