Lecture 11 Canker Sores Ladha

CANKER SORES:

• Recurrent aphthous stomatitis or ulcers (RAS or RAU)

• Superficial ulcerations on oral mucosa

o Ulcer has yellowish-white or grayish-white

pseudomembrane and red inflamed border

o Very painful and sensitive when palpated

• Can occur on soft palate, under tongue, floor of mouth,

on inside linings of lips (labia) and cheeks (buccal)

• Considered non-infectious

o Unknown causes but theories around: genetics,

stress, nutritional deficiencies, diet, hormonal

changes and allergies

• Generally harmless but can cause pain, eating issues and

rarely weight loss

o Can result in secondary bacterial infection

• Similar lesions may occur in those with systemic diseases

(Behcet’s syndrome, Crohn’s disease, celilac disease, HIV)

• Often confused with cold sores & chancre sores

TYPES OF CANKER SORES:

Minor • Most common form (70-95% of cases)

• Affects at least 15-20% of otherwise heathy people worldwide

• Small (< 1 cm), shallow, circular or oval ulcers;

• 1-3 lesions per episode; 2-8 episodes per year

• Heal within 2 weeks with little-to-no scarring

Major • 10-15% of cases; more likely in immunodeficient patients

• Larger (>1 cm), deeper ulcers; occur as 1-2 lesions

• Heal within weeks or months (higher recurrence: < 1 month)

• Painful, swallowing difficulties, and may have scarring

Herpetiform • 5-10% of cases

• Look like herpes labialis but no herpes virus can be cultured

• ≥ 10 pinpoint ulcers & vesicles which coalesce into larger lesions

• Can also occur on keratinized mucosa

NOTE: CHANCRE SORE IS NOT A CANKER SORE

• Occurs during primary stage of syphilis infection usually on genitals; highly infectious

• Red, painless sore that resolves after a few weeks then about 1-2 months later forms

white mucous patch

WHEN TO REFER:

• Exclude major or herpetiform aphthae

o Severe pain difficulty eating

o Ulcer > 1 cm diameter & deep; > 5 ulcers

o Ulcer lasts > 14 days; recurs 6-12 times/year

o Occur as myriad of pinpoint ulcers & vesicles

o Ulcers coalesce into large irregular lesions

o Scarring

• Exclude other medical conditions

o Fever, sore throat, swollen lymph nodes

o Ulcers on other parts of body (skin, genital, eye)

o Diarrhea with blood or mucus

o Large white patches on tongue or cheeks

o Ulcer is not easily distinguishable

o Weight loss

o Change in bowel habits

o Ulcers > 2 weeks (especially in tobacco users)

o Systemic disease

• Review possible drug causes

• If determine recurrent minor aphthous ulcers, then may

provide self-care options

RISK FACTORS:

• Stress (emotional and physical)

• Injury in oral cavity – bite, scratch, chemical trauma

• Genetics: 90% chance of RAS with 2 parents suffering vs.

20% chance when neither parents suffering

o Controversial: eat what your parents eat?

• Nutritional deficiency (iron, folate, zinc, vit B1,2,6,12)

• Food allergies (milk, mints, food additives)

• Meds (NSAIDs, BBs, alendronate, immunosuppressants)

• Sodium lauryl sulfate in toothphase

o However, one double-blind study says NSS

• Recently quit smoking (keratinization of mucosa)

• Immunosuppression (HIV disease)

GOALS OF DRUG THERAPY:

• To reduce pain

• To reduce duration of ulcer

• To prevent complications of canker sore

• To prevent recurrence

• BAD NEWS: very little reliable evidence that ANY drug

therapy is effective at doing any of the above

NON-PHARMACOLOGICAL INTERVENTION: first-line intervention

• Chew slowly and carefully

• Avoid sharp-edged scratchy foods (chips, crunchy-fried foods, crackers)

• Avoid foods that cause pain (acidic, salty, alcohol, chocolate)

• Salt-water rinses

• Replace old toothbrushes with splayed bristles (use soft toothbrush)

• Make adjustments to oral implements (braces, mouth guards)

• Avoid or reduce risk factors

MOUTHRINSES:

Antimicrobial • Quality of studies were poor

• May help to reduce duration & severity of pain of ulcer

• Increase # of ulcer-free days between recurrences

• Probably does not reduce the incidence of new ulcers

Chlorhexidine 0.1 to 1% (Rx)

• Reduced number of ulcer day index (sum of number of ulcers per day over a 5 to 6-week period)

o 7-10 fewer ulcer days over 5-6 weeks

• Increased number of ulcer-free days (22.9 vs. 17.5)

• May reduce duration of ulcer by < 1 day (NSS)

• Did not reduce incidence of new ulcers

• From one study, reduced pain from 49 to 24 on pain scale (50% but reduction), but another showed NSS

• SEs: bitter taste, brown staining of teeth/tongue, nausea

Hexetidine (OTC) • Not more effective than placebo at reducing ulcer incidence and duration, and severity of pain

Listerine • Thymol, eucalyptol, menthol, methylsalicylate = BID rinse

• No difference on ulcer incidence, duration or pain when compared to placebo

OTC THERAPY:

Little evidence of efficacy

• Local anesthetics: short duration of effect, and toxicity can occur with chronic or excessive use o Alternative use: abrasion of canker sore membrane with

cotton-tip soaked with anesthetic (RAS minor only!)

• Oral analgesics (ibuprofen, acetaminophen, ASA)

• Milk of magnesia

• OTC magic mouthwash

Protectants • Orabase (carboxymethylcellulose) & Zilactin (hydroxycellulose) may help to soothe, coat, and protect ulcer

Bleach-type mouth rinses

• Amosan (sodium perborate), diluted hydrogen peroxide can be used but may not be more effective than salt-water rinses o Sodium perborate may contain boron (toxic) o H. peroxide may theoretically inhibit healing

Vitamin B12 1000 mcg SL daily

• At end of 6-month trial: reduced ulcer duration, pain, average # of episodes per month, and # of pts with no ep in 6th month o Only started to see response after 4 months of txt

• Unknown mechanism

Lecture 11 Canker Sores Ladha

PRESCRIPTION:

Topical corticosteroid • Hydrocortisone, triamcinolone, betamethasone (studies from 1960s-80s)

• Trend to reduction of ulcer days index, reduction in severity of pain

• Inconsistent results in duration of ulcers, incidence of new ulcers

• Patients preferred topical steroids in general vs. placebo

• Risk of fungal and bacterial infections, systemic side effects NOTE: only triamcinolone in Orabase is available

Benzydamine • Only provided transient pain relief

Tetracycline rinse 250 mg QID • Reduced duration of ulcer and days of pain by 4 days

• Risk of fungal infections and developing bacterial resistance

• Do not use in children

Off-label • Oral corticosteroids, levamisole and thalidomide

• Reserved for refractory ulcers, the immunocompromised, or those with systemic diseases

IN SUMMARY:

• Review patient’s medical history, allergies and medications

• If RAS minor is determined, advise non-drug therapy first (disease is self-limiting & drug therapy is not necessarily going to improve outcomes)

• Choose therapy based on patient’s complaints

o Pain: oral analgesics, topical anesthetics, protectants, salt-water rinses, benzydamine (Rx), steroids (Rx)

o Ulcer duration: hexetidine, chlorhexidine (Rx), tetracycline rinse

o “Recurrence” – depends on patient’s definition: try Vit B12 at least 4 months

Lecture 11 Cold Sores Ladha

COLD SORES: aka herpes labialis

• Incidence: 1.6 per 1000 patients yearly

• Prevalence: 2.5 per 1000 patients yearly

• 1/3 of patients experience recurrence

o Most experience 2-3 eps/yr

• Primarily caused by herpes simplex virus type 1

(HSV-1) but sometimes HSV-2

SYMPTOMS:

• Primary infection CAN BE ASYMPTOMATIC!

• If symptomatic but otherwise healthy:

o Kids: gingivostomatitis

o Adults: pharyngeal involvement and/or

mononucleosis-like disease

o Vesicles occur on any part of oral mucosa

o Development of ulcerations

o Halitosis, fever, dehydration

o Heal within 2 weeks

• Immunocompromised: as above but large

necrotizing lesions possible

HSV-1 CYCLE:

• HSV-1 virus resides in latent stage in trigeminal

ganglion for lifetime

o Secondary infections may manifest as “cold

sores” during viral reactivation

• Prodromal tingling and burning might occur up to

48 hours before recurrent breakouts

o 16-25% prodromes don’t result in cold sore

• Vesicles (containing clear fluid) form on mucous

membranes and keratinized areas of lip

• Vesicles break, crust over, then heal with no

scarring in 7-10 days

• On mucus membranes, may form ulcers

COMPLICATIONS: uncommon in otherwise healthy pts

• Pain prevents drinking = danger of dehydration in

kids, especially with fever

• Kaposi Varicelliform eruption (super infection on

eczematous skin)

• Herpetic whitlow – on finger, thumb

• Conjunctivitis / keratitis

• Spread into respiratory tract or esophagus

• Encephalitis

WHEN TO REFER:

• Primary infection suspected

• First time oral lesion

• Excessive recurrence (> 6 times per year)

• Severely inflamed, contains pus, bleeding

• Duration > 14-21 days

• Systemic lymphadenopathy and fever

• Difficulty swallowing

• Seizures, stiff neck and vomiting

• Pregnant near-term woman

• Immunocompromised (presentation of recurrent

episode may be atypical)

RISK FACTORS:

• Sun exposure (UVB) especially with sunburn

• Physical trauma in oral cavity

• Stress or illness or fever

• Malnourishment, fatigue, menstruation

• Immunosuppression (HIV, chemotherapy)

GOALS OF THERAPY:

• Palliation of pain and reduce duration of lesions

• Prevent outbreaks (or at least try to)

• Prevent infection spread to self or others

PRIMARY INFECTION: unlike genital herpes, there is no standard drug therapy for treatment of 1st ep

RECURRENT INFECTIONS: self-limiting mild disease = drug therapy not necessary

NON-PHARMACOLOGICAL INTERVENTIONS:

• Avoid or reduce risk factors where possible

• Proper nutrition but avoid food/drink that cause pain

• Washing or topical application of medications should be gentle

• Minimize touching lesion and wash hands often; do not touch eyes

• Reduce spread of infection:

o Apply topical therapies with cotton swab

o Avoid sharing anything that touches lesion (chapstick, cup)

o Avoid kissing or oral sex during active lesions

THERAPY TO REDUCE PAIN/HEALING OF RECURRENT INFECTIONS:

Oral analgesics • Acetaminophen or ibuprofen may help reduce pain (no RCTs)

Topical anesthetics

• Tetracycline 1.8% six times/day: reduced time to scab loss + subj. benefits

• Lidocaine 2.5%, prilocaine 2.5%: decreased duration of eruptions & subjective symptoms

Topical barrier products

• Petroleum jelly, Zilactin, Lipactin, etc – no reliable RCTs

• May help soothe irritated tissues & prevent secondary bacterial infxn

• Prevent skin cracking and soften crusty lesions, anecdotally reduces pain

Zinc applied within 1 h of first sign of sx

• MOA: inhibit DNA synthesis and blocks viral-to-cell adhesion

• Zinc oxide (0.3% elemental Zn) + glycine cream q2h until crust forms or 21 days passed o Duration of lesions reduced but more burning & itching

• Zinc sulfate 1% gel applied q2h for 5 days

• Greater % of symptom-free patients

THERAPY TO TREAT RECURRENT INFECTIONS:

Topical antivirals • Acyclovir 5% cream applied within 1 h of first sign of sx (applied 5x/day)

• Inhibits replication = faster healing

• No decrease in pain duration or severity, may not abort lesions

• Ointments NOT EFFECTIVE = use CREAMS

Acyclovir 5% + HC 1% cream

• Reduces duration by 1.5 days (vs. 1 day when on acyclovir alone)

• Costs DOUBLE price of acyclovir 5% cream or docosanol

Bee propolis 3% oint applied 4-6 times daily

• Bee resin containing flavonoids & antioxidants purported to help fight infection and boost immunity

• May be contraindicated in asthmatics and those allergic to bee pollen

• May reduce duration by 3-4 days vs. placebo

Docosanol Abreva (docosanol 10%) cream costs $20-30

• Proposed mechanism = blocks viral entry into host cell unlike antivirals which inhibit replication

• Treatment must begin BEFORE lesion formation (within 12 hours of onset of prodrome signs and symptoms)

• May cause headache, burning/stinging site reaction

• No evidence for suppressive therapy

• Docosanol = acyclovir in efficacy o Reduces healing time, pain, itching, burning o When lesions do occur, may shorten the soft ulcer/crust stage

responsible for most of the pain and inflammation o Produces more aborted episodes than placebo o Treatment after lesions occur unlikely to be effective

Oral meds (all Rx)

• Antivirals o Acyclovir 400 mg 5 times daily x 5 days o Famciclovir 750 mg BID x 1 day or 1500 mg x 1 dose o Valacyclovir 2 g BID x 1 day or 750 mg BID x 1 day or

1500 mg x 1 dose

• Must take within 1 hour of onset of prodromal lesions

• May reduce duration of pain and lesion by 1 to 1.5 days

• May not abort lesions

Lecture 11 Cold Sores Ladha

THERAPY FOR PREVENTIVE TREATMENT OF RECURRENT INFECTIONS

Sunscreen • Use of sunscreen at least SPF 15 before exposure to UVB may prevent recurrent attacks o BUT one study showed no difference in incidence compared to placebo in 7 days

Lysine 500 mg daily to 1000 mg QID

• MOA: competes with arginine which virus needs for reproduction

• May prevent recurrence and possibly decrease severity and duration of outbreak

• Probably ineffective for treatment

• All studies were very small, old; no data for kids or pregnant women

• Concerns: nitrogen build-up in liver/kidney failure patient; potential kidney dysfunction

Topical antiviral • Impractical; must apply 2-4 times daily

• Evidence shows little-to-no benefit in preventing or delaying cold sores

Oral antiviral • > 6 episodes/year = suppressive treatment o Acyclovir 200 mg QID or 400 mg BID x 4 months o Valacyclovir 500 mg daily x 4 months

• Marginally more effective than episodic treatment? o Disease recurs after therapy = cost beneficial??

Lecture 11 Dry Mouth Ladha

SALIVA FUNCTION:

DIGESTION • Clear watery secretion containing digestive enzyme (ptyalin, amyase, lipase)

• Chewing, bolus formation, swallowing

• Maintains taste buds

PROTECTIVE • Lubrication aid (mucin)

• Buffering (electrolytes, pH balance)

• Antimicrobial components (Ig, enzymes)

• Washes, cleanses, lubricates, healing

XEROSTOMIA:

• Secondary to reduced or altered saliva production

• Subjective sx (ex// saliva flow can objectively be normal)

• Underlying medical condition or medications (see risk factors)

RISK FACTORS:

• Older patients (systemic disease + medications)

• Fluid loss (dehydration, vomiting, diarrhea)

• Head/neck cancer pts (apoptosis from radiation field & amount)

• Graft -vs-Host Disease (allogenic BMT)

• Sjogren’s syndrome

• HIV infection (gland enlargement)

• Brain damage

• Mouth breathing (ex// dyspnea or airway obstruction at EOL)

• Positive airway pressure machines (ex// CPAP, BiPAP)

• Tobacco (smoke, chew)

• Many common medical conditions (HTN, diabetes, depression,

anxiety, hyperlipidemia)

MEDICATION-INDUCED XEROSTOMIA: most common cause

Anticholinergics Ipratropium, atropine, scopolamine, dimenhydrinate

Antidepressants Amitriptyline

Benzodiazepines Clonazepam

Antihistamines Diphenhydramine

Antipsychotics Loxapine, quetiapine

Diuretics Hydrochlorothiazide, furosemide

Antispasmodics Oxybutynin, tolterodine

Recreational drugs Cannabis

CONSEQUENCES OF HYPOFUNCTIONING SALIVA GLANDS:

Discomfort Sore throat, difficulty chewing and swallowing, pain, nausea, difficulty talking

Disease Dental caries, candidiasis, gum disease, malnutrition, denture sores, ulcers, loss of taste, halitosis, insomnia

QUESTIONS:

History • Age?

• Medical conditions?

• Medications? Herbals?

• Radiation?

• Chemotherapy?

• Recreational drugs?

• Sleep apnea?

• Mouth-breathing?

• CPAP device?

• Diet? Caffeine-intake? Smoker?

Check QOL • How much water do you drink?

• Do you have difficulty swallowing, talking, chewing, etc?

• Do you have dry eyes? Toothache? Mouth ulcers, sores, pain?

COMFORT MEASURES AND PREVENTION OF DENTAL CARIES:

Identify and treat underlying cause

Oral hygiene • Restrict sugars, acids, alcohol

• See dentist

• Use fluoridated toothpaste or antimicrobial mouth rinses (without alcohol)

• Regular brushing and flossing

Maintain good water-intake

• Sipping small amounts of water or sucking on ice chips frequently

Lubricate lips • Vaseline, lip balm (unflavoured, non-minty), glycerin

Tastier food • Add herbs, condiments, fruits to make food more tastier

Avoid harming or irritating mouth

• Hard, sharp-edged foods

• Acidic, spicy, alcohol

If salivary glands functional

• Chew on applies, celery, carrots or gum to mechanically stimulate glands

MANAGEMENT OF XEROSTOMIC MEDICATIONS:

• Switch to a less xerostomic drug (ex// TCA to SSRI)

• Take xerostomic drug during daytime

o Saliva output is lower at night

o Unaware of symptoms during sleep

• Divide up daily drug dose to reduce side effects

PRESCRIPTION TREATMENT:

PILOCARPINE:

Use • Indicated for Sjogren’s syndrome & radiotherapy patients

Dosage form

• Salagen 5 mg oral tablets TID-QID (max 30 mg)

• Isopto-carpine eye drops can be used orally but measuring is difficult & overdosing more difficult to prevent

SEs • Sweating, nausea, headache, dizziness, arrhythmias, diarrhea, lacrimation, respiratory problems

CIs • Asthmatics, heart disease, GI disorders, narrow angle glaucoma & acute iritis

Overdose • May need atropine and epinephrine if overdose

YOHIMBINE:

Use • Off-label use

• Alpha-2 blocker with cholinergic effect

• Don’t recommend yet until more large scale studies available

Evidence • Small study of 10 antidepressant-treated pts showed improved salivation when taking 6 mg TID for 5 days

• Increased saliva production when compared with anetholtrithione 25 mg tid (3.5 fold vs. 1.5 fold)

SEs • Hypotension, nausea, flushing, diarrhea, headache

OTC TREATMENT:

ANETHOLTRITHIONE: 25 mg tabs (1-2 tabs TID)

MOA • Bile-secreting stimulating agent

• Stimulates parasympathetic nervous system and increases ACh secretion

Evidence • Increased saliva flow rate by 75% in 2 weeks

• Oral discomfort improved or resolved in 83% of pts on AT vs. 20% on saliva substitute in 4 weeks

• More helpful in drug-induced xerostomia but less effective in oral cancer therapy patients

SEs • Abdominal discomfort and flatulence

• Long-term safety data lacking

SALIVA SUBSTITUTES:

• Replacement therapy to temporarily provide moisture and relief up to 1 hour

• Convenient for traveling and night-time use

• Use before meals to help soften up food and aid in chewing

• More palatable than water

• To mimic saliva, may contain viscosity agents (carboxymethylcellulose),

calcium and phosphate ions, lactoferrin, lactoperoxidase, glucose oxidas &

lysozyme

Lecture 11 Dry Mouth Ladha

DRY MOUTH PRODUCTS:

Product Substitution Stimulation

Biotene (gum, toothpaste, mouth rinse, denture paste)

Lactoferrin, lactoperoxidase, glucose oxidation, lysozyme, hydroxycellulose Xylitol

Moi-stir Carboxymethocellulose, KCl and NaCl Sorbitol

Mouth-Kote Yerba sante mucopolysaccharide Xylitol, sorbitol, citric acid, ascorbic acid

Oral-balance Lactoferrin, lactoperoxidase, glucose oxidase, lysozyme, hydroxyethylcellulose Xylitol

SalivaSure Carboxymethylcellulose, calcium, phosphate Xylitol, citric acid, apple acid

Lemon-glycerin swabs Glycerin Citric acid

Sugarless gum Xylitol, mannitol, sorbitol, maltitol, etc…

Lecture 11 Halitosis Ladha

HALITOSIS:

• Bad breath

• May affect up to 30% of ppl regardless of age

CAUSES:

Intra-oral (90%)

• Anaerobic (generally) bacteria

• Chronic teeth & gum disease

• Acute oral infection

• Volatile sulphur compounds (VSC)

• Xerostomia

• Improperly cleaned dentures

Extra-oral

Nose/ throat

• Post-nasal drip

• Sinusitis

• Nasal foreign bodies

• Tonsiloliths

Resp • Chronic bronchitis

• Cancer

GI • GERD

Metabolic • Ketoacidosis

• Renal/hepatic failure

Other • Halitophobia

• Foods (spice, garlic)

• Tobacco

CONSEQUENCES:

• Source of embarrassment

• Chronic exposure to VSCs = toxic?

o Worsen oral infections

o Contribute to heart disease &

inflammatory diseases

o Contributes low birth weight

• Indication of more serious underlying disorder

such as periodontic disease

• Difficulties

o Subjective

o Person suffering may not noticed it

o Difficult to determine source

TONGUE BACTERIA:

• Tongue papillae ideal environment for growth

of bacteria & formation of tongue coating

• Oral bacteria live on dorsum of tongue and

periodontal pocket

• Lyse cysteine, cystine and methionine amongst

other amino acids

• Bacteria break down epithelial cells, saliva and

serum proteins, food debris = produce volatile

compounds (VSCs, diamines, phenyl)

• Coating also includes epithelia, food debris

and saliva proteins

• Those with heavy yellow or gray tongue

coating associated with higher subjective and

objective “bad” breath sores

• Patients with halitosis were associated with

larger diversity of bacteria unique to sufferers

(ex// Solobacterium moorei) bacteria

associated with feces, bacteremia

ASSESSMENT:

• Subjective assessment (ask friends/loved ones)

• Organoleptic assessment (breath assessor)

• Halimeter device (detects & quantifies VSCs)

• Gas chromatography

• Saliva microbial load (culture)

• Saliva VSC production (in vitro)

• Review medical conditions and drug therapies that cause dry mouth or bad breath

REFERRAL: to dentist or physician

• Scraping of tongue reveals red flat lesion or bleeding (cancer, candida, leukoplakia)

• Dental disease or infection

• Metabolic, renal, hepatic disorders

• Pain, fever, enlarged glands or lymph nodes

• Other extra-oral causes

MANAGEMENT:

• Treat underlying cause if any

• General dental and oral hygiene

o Proper and regular flossing, brushing

o ↓ consumption of malodorous foods

o Regular low calorie fluid-intake (plain water)

o Regular mouth rinses, gargling and gum-chewing

o Avoid long-term use rinses with high alcohol content or antibacterial agents

TONGUE-SCRAPERS:

• Small weak studies; no long-term follow-up; no comparisons to mouthrinse or combo

• Neither studies measured breath subjectively

o Tongue-scraper reduced VSC levels by 40-75% (vs. toothbrush = 33-45%) and up to

25 mins (vs. toothbrush = 20 min)

• SE = triggers gag reflex and injury to papillae

MOUTHRINSES: most mask odor

Hydrogen peroxide 1.5%

• No RCTs

• Higher % may be toxic to cells inhibiting healing

Hexetidine • Little data

Listerine • Effective against plaque but little data against halitosis (EtOH content?)

Chlorhexidine 0.12% rinse (15 mL for 1 min)

• Effective BUT consider SE = tooth staining, bitter taste, taste changes, epithelial irritation and desquamation o CHX reduced VSC levels by 28% at 1 h but increased to 11% above

baseline after 5 hours o At 1 h mark, CHX reduced bacterial count from baseline by up to 30%

and was 50% lower than saline rinse o Effect was generally maintained after 5 hours o No subjective measure available

Various rinses 15 mL BID x 4 days

• Included Listerine, triclosan, cetylpyridinium, CHX, hydroalcholic control o Subjective breath analysis unavailable

• After 4 days o CHX 0.12% and 0.2% reduced VSC levels by 63% and 69% respectively

from baseline o All other rinses reduced VSC levels by 13-29% from baseline but NSS o Hydroalcoholic control increased VSC levels by 21% from baseline

• Plaque formation (side benefit) o CHX better than listerine, hydroalcoholic control o Cepacol (cetylpyridinium) and Plax (triclosan) = no change

SUMMARY:

• Investigate underlying cause of halitosis first

• Encourage use of non-drug measures

• Combine with mouth rinses

o Use non-CHX rinses first as generally safer choices

o CHX rinse if refractory but need Rx