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Slide 1: Sialadenitis/Parotitis/Sjogren’s pancreas Vincent Steniger, D.M.D 4-17-08
Slide 2: Outline Case presentation  Sialadentitis/ Overall Salivary Gland Infections  Parotitis  Sjogren’s Syndrome 
Slide 3: Chief 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
Slide 4: History of Present Illness  Current Medical Conditions: – Diabetes Type II (1995) – Asthma (1994) – Hx of Submandibular  Current Medications: – Glucotrol (5mg/day) (Stimulates Salivary Stones and Swelling and resection of SM glands in 1987 – Hx of both R & L Parotid Swelling, sometimes with Pain – GERD (2007) pancreas to secrete insulin. Sulfonoylurea  Blocks K+ in Islet Cells leading to greater increase in Insulin Secretion) – Prevacid 911  (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
Slide 5: Past Medical Hx (SHH)  HEENT – Pt wears glasses – Seasonal Allergies Endocrine: – Diabetes Type II – SM Glands Removed (1987) – Hx of R and L Parotid  CV System: – Pt denies Prosthetic Valve, Congenital Heart Disease, RF, Endocarditis    Swelling and Pain possible Sjogren’s – Hx of minor gland above the L. eye removed (1999) (Lacrimal)  Respiratory: – Asthma Gastro-intestinal/Hepatic: – GERD – Gall Bladder removal (1984) Renal: – Hx of Proteinurea   Urinary/Reproductive: Ø Dermatological: Ø Infectious: – Denies HIV/AIDS, Hep A, B, C, TB   Autoimmune: Ø Neoplastic: Ø
Slide 6: EOE/ 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
Slide 7: Sialadentitis  What is Sialadentitis? – Simply inflammation of the salivary glands – Can be due to a number of factors including:  Mumps infection  Coxacki Virus  Parainfluenza  Systemic Disease
Slide 8: Sialadentitis: 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
Slide 9: Parotitis    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
Slide 10: Parotitis: 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 mumpslike episodes in a young child are indicative. Sarcoidosis: Chronic nontender swelling of parotid gland occurs
Slide 11: 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
Slide 12: Mumps
Slide 13: Mumps: (Viral Parotitis)   Acute sialadenitis caused by RNA virus – Paramyxovirus Other viruses causing salivary gland infection: – – – Cytomegalovirus Coxsackieviruses Echovirus
Slide 14: Mumps: 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
Slide 15: Clinical 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
Slide 16: Mumps: Histopathology There is infiltration with plasma cells and the lymphocytes  The ductal lumens contain desquamated cell debris and leukocytes 
Slide 17: Mumps: Treatment There no effective antiviral therapy available for the treatment of mumps.  Analgesics and antipyretics are given to control pain and fever  Liquid diet with vitamins  Bed rest 
Slide 18: Sjogren’s Syndrome
Slide 19: Sjogren’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
Slide 20: Sjogren’s Syndrome  Sjogren’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
Slide 21: 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
Slide 22: Sjogren's Syndrome: Age of Onset The frequency distributions of ages at onset of symptoms & at diagnosis of primary Sjogren's syndrome 45 % OF PATIENTS 40 35 30 25 20 15 10 5 0 Onset At diagnosis 1-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 AGE
Slide 23: Sjogren’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
Slide 24: “Crocodile Skin” Tongue, Carious Teeth
Slide 25: Tests and Studies: Scintigraphy  Scintigraphy (Nuclear Medicine)  administer radioactive substance in order to show the physiology and state of the biological process: Scintigraphy Normal Moderate Marked diagnosis involvement involvement Degree of None Mild Severe xerostomia Salivary flow 1.60 0.42 0.00 rate (ml/5-min/ gland)
Slide 26: Scintigraphy: Continued  With Sjogren’s Syndrome there will be delayed uptake and concentration of marker as well as delayed excretion
Slide 27: 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
Slide 28: Tests and Studies: Serology Autoantibodies Rheumatoid factors (Igs) II) Cryoglobulins (type % positive 80 30 Ro/SSA La/SSB a-fodrin 60 30 95
Slide 29: Tests and Studies: Salivary Gland Biopsy  A lip biopsy, if positive for Sjogren’s will show lymphocytes clusters and glandular destruction due to inflammation
Slide 30: Tests and Studies: Salivary Flow Rate Stimulated  Unstimulated 
Slide 31: Sjogren’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)
Slide 32: Sjogren’s Syndrome: Differential Diagnosis       HIV, HCV infection Sarcoidosis Amyloidosis Lipoproteinemia Chronic graft-versus-host disease Lymphoproliferative disorders
Slide 33: Sjogren's Syndrome Algorithm for the diagnosis Dry mouth Dry eyes or Salivary gland enlargement or Raynaud’s phenomenon Purpura Renal tubular acidosis If any positive Eye & salivary gland tests Serology If positive Sjogren's Syndrome
Slide 34: Sjogren’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
Slide 35: Pathophysiology: 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
Slide 36: Parotitis/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
Slide 37: Normal
Slide 38: Pathological
Slide 39: Sjogren’s Syndrome: Systemic Manifestations Systemic manifestations Frequency (%) Arthralgia/arthritis Raynaud’s phenomenon Purpura/Vasculitis Lung involvement (increased liver enzymes) 60 30 15 (1) 10 (25) 8 (25) 5 1 Kidney involvement (Interstitial Nephritis/Glomerulonephritis) Liver involvement Muscle involvement Skopouli et al., Semin Arthritis Rheum. 2000, 29:296
Slide 40: “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 al  Cohort Study 
Slide 41: Why Do the 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
Slide 42: Purpose 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
Slide 43: Materials 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
Slide 44: Materials and 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
Slide 45: 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 
Slide 46: 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%
Slide 47: Conclusion 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 
Slide 48: Case Study Recurrent Parotitis as a First Manifestation of Adult Primary Sjogren’s Syndrome  Sugimoto et al  The Japenese Society of Internal Medicine January 17th, 2006  Case Report 
Slide 49: Case 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)
Slide 50: Salivary Function and Biopsy  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 
Slide 51: Conclusion     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
Slide 52: 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
Slide 53: To Do For The Patient: Refer to Sjogren’s specialist  Blood tests for Anti-SS-A(Ro), Anti-SSB(La) and Rheumatoid Factor  Stimulated, Unstimulated Salivary Flow  Minor Salivary Gland Biopsy  Confirm Dx of Sjogren’s Syndrome 
Slide 54: Sjogren’s Syndrome: Treatment   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
Slide 55: Treatment: 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