Aging and Diseases of the Salivary Glands Biology of Salivary Glands Domenica G. Sweier DDS June 4, 2003

2 Saliva  Frustrating for the dental team yet necessary for the patient!

June 4, When there is not Enough  Too little saliva can significantly alter a person’s quality of life and the morbidity associated with multiple systemic conditions How little is too little? What affects the quality and quantity of saliva production and flow?

June 4, 20034

5 Objective vs Subjective  Objective Major gland secretions  Resting flow rate with a Carlson-Crittenden Cup Minor gland secretions Whole saliva  Stimulated flow rate with citric acid, wax  Subjective Complaints of dry mouth (xerostomia) Questionnaire Thirst The “cracker” test

June 4, Xerostomia  Commonly referred to as “dry mouth”  Diminished salivary flow rate, typically accepted as a 50% decrease in the clinically determined rate in healthy individuals not taking medications Resting Flow Rate ml/min Stimulated Flow Rate 1-2 ml/min

June 4, Clinical Signs/Symptoms of Xerostomia  Dryness of mucous membranes  Tongue fissuring and lobulation (scrotal tongue)  Angular cheilosis/cheilitis  Fungal infections  Prosthesis-induced stomatitis  Amputation caries  Thick, ropey saliva  Dysphagia  Dysgeusia  Difficulty eating/speaking/ wearing prosthesis  Swelling of the salivary glands  Difficulty expressing saliva  Cheek biting  Persistent need for fluids  Burning tongue

June 4, What Contributes to Xerostomia?  Aging Hormonal Changes/Menopause  Disease Local Systemic  Environmental Insults/Trauma  Medications

June 4, Aging  Salivary Quantity in Health No changes in major secretions (parotid, submandibular) No changes in minor secretions  Salivary Quality in Health No general changes in salivary constituents

June 4, Aging  If the quality and quantity of saliva doesn’t change with age, then what accounts for the increased incidence of xerostomia and associated morbidity among the elderly? Medications, diseases, and other environmental insults affect both the quality and quantity of saliva  An increase in incidence of these insults generally associated with an increase in age

June 4, Menopause  Average age of onset of menopause in USA is 50 years  Oral symptoms common, particularly among those with systemic complaints  Cross-sectional and longitudinal studies have failed to provide significant and reproducible evidence that salivary flow is affected by menopause Oral complaints most likely the result of the types and numbers of xerostomic medications taken  Anti-hypertensives, anti-depressants, and anti-histamines are common in this group

June 4, Diseases/Environmental Factors  Diseases Local Systemic  Environmental Factors Head and Neck Radiation Chemotherapy Medications

June 4, Local Diseases  Tumors/Growths Benign Malignant  Obstructive Diseases Calculi, mucus plugs Unusual anatomy  Inflammatory Diseases Acute viral sialadenitis Acute and recurrent bacterial sialadenitis Inflammation/Infection secondary to systemic disease

June 4, Tumors/Growths  Primary benign and malignant tumors Determine whether benign or malignant since they are treated differently Incisional biopsy for definitive diagnosis Smaller the involved gland, more likely malignant  Malignant Seek medical attention for swelling under the chin or around the jawbone, if the face becomes numb, facial muscles do not move, or there is persistent pain Usually treated with a combination of surgery and radiation

June 4, Obstruction: Sialolithiasis  Calculi form in the duct, blocking the egress of saliva Majority in submandibular gland  Painful swelling which increases at meal time  Bi-manual palpation in submandibular gland  X-ray, sialography, CT, ultrasound  Analgesics, try to push stone out, may need to dilate orifice to remove

June 4, Submandibular Calculi

June 4, Unusual Anatomy  Unusual anatomy in the gland manifested as strictures in the duct system Recurrent obstruction with associated pain and inflammation of glands Pooling of saliva leading to secondary infection  May need surgery to remove affected area of gland or entire gland

June 4, Inflammation/Infection: Viral  Mumps is the most frequent diagnosis of acute viral sialadenitis Member of the paramyxoviridae Mostly in parotid The incubation period is 2-3 weeks Acute painful swelling and enlargement Fever, headache, loss of appetite Most common in children Very effective vaccine

June 4, Inflammation/Infection: Bacterial  Types Acute suppurative bacterial sialadenitis  Commonly S. aureus, S. viridans, H. influenzae, E. coli Chronic recurrent sialadenitis  May be secondary to some type of obstruction or unusual anatomy  May be due to resistant organism; culture to determine  Treatment Antibiotics and analgesics Rehydrate and stimulate saliva May need open drainage/surgery

June 4, Bacterial Parotiditis

June 4, Systemic Diseases  Sjögren’s Syndrome  Sarcoidosis  Cystic Fibrosis  Diabetes  Alzheimer’s Disease  AIDS  Graft vs Host Disease  Dehydration

June 4, Sjögren’s Syndrome  Autoimmune disorder affecting lacrimal and salivary glands Xerostomia and keratoconjunctivitis sicca  Primary and Secondary disease The latter associated with another autoimmune disorder such as RA, SLE, etc.  Dense inflammatory infiltrate with destruction of glandular tissue  Treatment is palliative

June 4, Sarcoidosis  Unknown cause; believed to be alteration in cellular immune function and involvement of some allergen  Any organ but most often the lungs; can affect the parotid gland  Granulomatous inflammation  Most often drugs of choice are corticosteroids

June 4, Cystic Fibrosis  Faulty transport of sodium and chloride from within cells lining lungs and pancreas to their outer surface  Causes production of an abnormally thick sticky mucus  Obstruction of pancreas leads to digestive problems; inability to digest and absorb nutrients  Gene has been identified and cloned  No known “cure” therefore palliative treatment

June 4, Diabetes  Uncontrolled blood glucose levels may contribute to xerostomia  Medications may induce xerostomia  May get enlargement and inflammation of parotid glands (common in endocrine diseases)  Difficulty to ward off infection: candidiasis, gingivitis, periodontitis, and caries

June 4, Alzheimer’s Disease  A neurodegenerative disorder leading to a decrease in cognition and mobility  May affect the neurological component to salivary production and/or flow  Xerostomic medications Complicated by behavior which makes it difficult to maintain a healthy dentition  Poor oral hygiene  Poor cooperation for dental care and treatment in a conventional setting

June 4, AIDS  HIV-Associated Salivary Gland Disease (HIV-SGD) Enlargement of the major salivary glands Xerostomia Some similarities to autoimmune diseases HIV itself not consistently found to be in glandular tissue  Medications

June 4, Graft vs Host Disease (GVHD)  Immune cells of an allogenic transplant attack recipient  Acute, 100 days  Major cause of morbidity and mortality  Initial presentation as a red rash  Salivary gland involvement with swelling and inflammation  Progresses quickly to life-threatening condition  Treat by increasing immunosuppression

June 4, Dehydration  Defined as the loss of water and essential body salts (electrolytes) needed for body function Sweating, diarrhea, emesis, blood loss, etc.  Symptoms include flushed face, dry, warm skin, fatigue, cramping, reduced amount of urine  Oral signs/symptoms Xerostomia, dry tongue Thick, sticky saliva Dry, cracked lips (cheilosis)

June 4, Head and Neck Cancer: Radiation Therapy  Goal is to kill cancer cells  Measured in Gray (Gy) units of absorbed radiation: 1 Gy = 100 cGy = 100 rads  Can be used alone or combined with surgery and/or chemotherapy  Three main routes External beam (most head and neck) Brachytherapy (body cavities) Interstitial

June 4, Radiation Dose  Dependent on tumor tissue/type  Average of 200 cGy daily for 5 consecutive days with two days of rest  Total cummulative dose ranges from 5000 cGy to 8000 cGy for advanced tumors  Threshold of permanent destruction is cGy

June 4, Tissue Response  25 Gy: Bone marrow, lymphocytes, GI epithelium, germinal cells  Gy: Oral epithelium, endothelium of blood cells, salivary glands, growing bone and cartilage, collagen  Doses > 50 Gy: bone and cartilage, skeletal muscle

June 4, Tissue Changes  Irradiated tissue becomes hypocellular, hypovascular, and hypoxic resulting in fibrosis and vascular occlusion  The destruction is mostly permanent Irradiated tissue does not re-vascularize with time  As a result, irradiated tissue does not heal well after injury

June 4, Common Side Effects: Systemic  Nausea  Vomiting  Neutropenia  Alopecia  Fatigue

June 4, Common Side Effects: Oral  Mucositis and Dermatitis  Dysphagia  Dysgeusia  Trismus  Osteo- and soft tissue necrosis  Xerostomia Fungal infections Radiation Caries

June 4, Radiation: Xerostomia  Parotid gland is more susceptible than the submandibular or sublingual glands  See a slight improvement after therapy but will soon plateau at a lower level than pre- therapy  Result is thick, ropey saliva, decreased in amount, with markedly diminished lubricating and protective qualities

June 4, Radiation: Mucositis  The oral eipthelium will get a “sun burn” like inflammation  This will be exacerbated by the lack of the lubricating properties of saliva  The result will be a red, irritated, dry mucosa

June 4, Saliva Post-Radiation

June 4, Mucositis

June 4, Radiation Caries

June 4, Prosthesis-Induced Stomatitis

June 4, Fungal Infections

June 4, Scrotal Tongue

June 4, Chemotherapy  Is given orally, IV, by injection (SQ, IM, IL), or topically in cycles depending on the treatment goals (type of cancer, how your body responds, how well you body recovers, etc.)  Affects all rapidly dividing cells Many side effects in all body systems  Oral complications from direct damage to oral tissues secondary to chemotherapy and indirect damage due to regional or systemic toxicity Frequency and severity related to systemic immune compromise, i.e. myelosuppresion

June 4, Chemotherapeutics  Drugs commonly associated with oral complications Methotrexate Doxorubicin 5-Fluorouracil (5-FU) Busulfan Bleomycin Platinum coordination complexes  Cisplatin  Carboplatin

June 4, Tissue Damage  The propensity of chemotherapy to damage tissue, specifically oral tissues, is dependent on each individual drug and its ability to induce myelosuppresion (neutropenia)  Drugs differ on the timing of myelosuppresion Consider this when treating patients undergoing chemotherapy  Tissues, oral tissues, return to pre-chemotherapy state when allowed time to heal after therapy

June 4, Common Side Effects: Systemic  Fatigue  Nausea  Constipation  Diarrhea  Hemorrhage  Anemia  Neutropenia  Pain  Alopecia  Peripheral neuropathy  CNS disturbances  Fluid retention  Bladder and kidney problems

June 4, Common Side Effects: Oral  Mucositis (ulcerative)  Reactivation of HSV  Dysgeusia  Dysphagia  Infections Fungal Periodontium periapices  Neuropathies  Salivary gland dysfunction/toxicity xerostomia

June 4, Summary  While there appear to be many insults leading to salivary hypofunction, healthy aging does not appear to be one of them  The main insults leading to salivary gland damage and/or hypofunction are Disease  Local  Systemic Environmental insults/trauma  Radiation  Chemotherapy Medications