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Home , Amlexanox, Aphthous stomatitis, Desquamative gingivitis, Fluocinonide, Glossitis, Lichen planus

Contemporary

Leticia Ferreira, DDS, MS Department of Dental Practice Arthur A. Dugoni School of Dentistry University of the Pacific 7385 Patients Disease Frequency (BCD, July 2010) planus (897) 12.1% (799) 10.8% Chronic (741) 10.0% Sjogren’s syndrome (431) 5.8% Aphthae & other ulcerations (501) 6.8%

Allergic reactions (262) 3.5% Burning syndrome (295) 3.9%

Mucous membrane (199) 2.7% (156) 2.1% Migratory (130) 1.7% Oral (50) 0.7% TOTAL (4461) 60.4% Miscellaneous Disorders (BCD, July 2010) 49 Graft vs. host disease 30 erythematosus 16 multiforme 13 Proliferative verrucous 10 9 Chronic ulcerative 8 8 Langerhans cell histiocytosis 4 Epidermolysis bullosa 4 3

• Immunologically (T-cell) mediated disorder • Middle-aged females • Affects both and • Skin: purple, pruritic, polygonal • Oral – Reticular • Wickham’s striae – Erosive (ulcerative) – Atrophic – Bullous – Plaque-like – Papular (Eisen, 2002) (Lodi et al 2005) (Lozada-Nur 1997) Lichen Planus Oral Lichen Planus (BCD, July 2010) Based on 897 patients

• 76.5% Female average age 57.2

• 23.5% Male average age 51.8

• Combined average age 56.0 Lichen Planus Oral Lichen Planus (BCD, July 2010) Based on 897 patients

• Skin 14%

• Genitalia 2.3% Lichen Planus Lichen Planus Clinical Sites (BCD, July 2010)

• Buccal Mucosa 62.8% • Gingiva 55.8% • 33.2% • 8.4% • 7.0%

• Gingiva only 20.6% • Buccal Mucosa only 12.4% Desquamative • Lichen planus • Pemphigus • Pemphigoid • – – Cinnamon – Preservatives Lichen Planus

• Diagnosis

– Clinical Appearance • Presence of white striae bilaterally on posterior buccal mucosa – Histopathologic examination • Erosive cases • Isolated lichenoid (in order to rule out premalignancy or – Immunofluorescence • In order to rule out Pemphigus and Pemphigoid, and chronic ulcerative stomatitis Lichen Planus • Treatment –Only for symptomatic patients • Topical • Systemic corticosteroids • • Cyclosporine • and –Patients should be evaluated at least once a year

(Lodi et al 2005) (Al-Hashimi et al 2007) Lichen Planus

• High Potency Topical Rx: gel 0.05% (Lidex) Disp: 15gm tube Sig: Apply to affected area 4x/day. Do not eat or drink for 45 minutes after application • Highest Potency Topical Corticosteroid Rx 0.05% gel (Temovate) Disp: 15 gram tube Sig: Dry the area and apply a small amount 3-4x/day. Do not eat or drink for 45 minutes after application. • Widespread gingival involvement: – “suck-down” tray filled with gel and used 2x/day for 15-20 min Lichen Planus

• Systemic Corticosteroid Rx 10 mg tablet Disp: 40 tabs Sig: Two tabs bid x 7 days, then 1 tab bid X 4 days, the 1 tab daily until gone Lichen Planus

• Side-effects of topical corticosteroid therapy: –Candidiasis Lichen Planus

• Combined Topical Therapy – Topical corticosteroid + 10 mg Troche 1-3xs daily or Nystatin Oral Suspension 1 tsp 2xs daily Lichen Planus

• Pre-malignant potential?? – Controversial issue – Clinical studies and case reports suggest that OLP patients are at a greater risk of developing OSCC • Great variation in source of data, inclusion criteria, length of follow-up and design – Lichenoid dysplasia vs. lichen planus – Large independent controlled retrospective studies have shown a significant risk • 1% over a 5 year period – A minimum of one follow-up visit per year is recommended

(Markopoilos et al 1997) ( Lo Muzio et al 1998 ) (Fang et al 2009) (Gandolfo et al 2004) (van der Meij et al 1999)(Al-Hashimi et al 2007) Be suspicious of a that looks like lichen planus but is localized to the lateral border of the tongue Early dysplastic changes, when the starts to become atypical or dysplastic but is not invasive yet, can evoke a lichenoid reponse of the body’s immune system ag Lichenoid Reactions

• Most common lichenoid reactions: – Non-steroidal anti-inflammatory drugs (NSAIDs) – Antihypertensives – Cinnamic aldehyde flavoring – Mercury

(Miller et al 1992) (Allen & Blozis 1988) (Issa et al 2005) (Moller 2002) Lichenoid Reactions (BCD) 63 patients (04/05) • NSAIDs 19 • Cardiovascular drugs 10 • Mercury (amalgams) 10 • Cinnamic aldehyde 9 • Antidiabetics 9 • Anti-lipemic 4 • Gold salts 2 Drugs causing lichenoid drug reaction

Allopurinol Gold Practolol Amiphenazole Hydroxychloroquine Propanolol Atorvastatin (Lipitor) Captopril Labetanol Quinidine Carbamazetine Mercury Quinacrine Chloroquine Spironolactone Chlorpropamide Metopromazine Streptomycin Cyanamide NSAID Oxyprenolol Thiazides Enalapril Palladium Tolbutamide Erythromycin Para-amino salicylate Triprolidine Penicillamine Zoloft Furosemide Phenothiazines Candidiasis

• • Dimorphism: yeast and hyphal forms • Most common oral fungal Candidiasis

• Predisposing factors:

’ – therapy – Newborns immature immune system – Cancer chemotherapy – Advanced malignancy – Corticosteroid therapy – Xerostomia – Dentures – Immunocompromised – Diabetes mellitus states – Pregnancy • HIV/AIDS • Transplant patients – Iron deficiency Candidiasis • Pseudomembranous candidiasis – “Thrush” – White material that can be wiped off – Erythematous mucosa underneath – Burning sensation – Metallic taste Candidiasis

• Erythematous “acute atrophic” candidiasis – Often associated with • “Antibiotic sore mouth” – Painful – Loss of filiform papillae on tongue Candidiasis

• Chronic atrophic candidiasis – “Denture stomatitis” – Erythematous mucosa – Palate and maxillary alveolar ridge – Usually asymptomatic Candidiasis

• Angular – Labial commissures – Erythema, fissuring and scaling – Reduced vertical dimension Candidiasis

• Mucosal smear and tissue culture • Oral therapy – Nystatin oral suspension, pastilles or ointment • Systemic antifungal therapy – Fluconazole (Diflucan) – Ketoconazole Recurrent (recurrent aphthous ulcerations) “canker sores” • Very common: 20% – Affects children and young adults more frequently • Unknown etiology – The cause appears to be “different things in different people” • Immune mediated, self-limiting ulceration – CD8 T-cells produce cytokines which lyse epithelial cells Recurrent Aphthous Stomatitis (recurrent aphthous ulcerations) “canker sores” • Trauma (dental • Immunologic factors procedure) • AIDS • Emotional stress • Endocrine imbalance • Nutritional deficiencies • • Socio-economic level Infectious agents • Genetic predisposition • • Chemicals in food • Smoking cessation Recurrent Aphthous Stomatitis (recurrent aphthous ulcerations) “canker sores”

• Minor

• Major

• Herpetiform Recurrent Aphthous Stomatitis (recurrent aphthous ulcerations) “canker sores”

• Minor aphthae (80%) – Childhood to adolescents – ↑ Females – Less than 1 cm – On moveable mucosa (not covering bone) – Painful with erythematous border – Heal spontaneously in 7 to 14 days w/o scarring Recurrent Aphthous Stomatitis (recurrent aphthous ulcerations) “canker sores”

• Major aphthae (10%) – Larger than 1.5 cm – Deeper than minor aphthae – ↑↑ , tonsillar , and labial mucosa – Can take several weeks to months heal – May cause scarring Recurrent Aphthous Stomatitis (recurrent aphthous ulcerations) “canker sores” • Herpetiform aphthae (10%) – Adulthood – 1 to 3 mm occurring in clusters – Any oral mucosal site may be involved – vs. – Heal in 7-10 days Recurrent Aphthous Stomatitis (recurrent aphthous ulcerations) “canker sores” • Diagnosis: – Diagnosis by history and clinical features – shows nonspecific ulceration – Patients with severe disease: • Rule out systemic causes • Patch tests for stimuli • Elimination of potential : – Sodium lauryl sulfate in toothpaste – NSAIDs, various beta blockers, nicorandil – Streptococci, Helicobacter pylori, HSV, VZV, and CMV – Many foods: cheese, coffee, cow’s milk, gluten, nuts, strawberries, tomatoes, flavoring agents, preservatives Recurrent Aphthous Stomatitis (recurrent aphthous ulcerations) “canker sores” • Treatment: – High-potency topical – – 5% (Aphthasol) Recurrent Aphthous Stomatitis (recurrent aphthous ulcerations) “canker sores” Rx Fluocinonide gel or cream 0.05% (Lidex) Disp: 15 or 30 gram tube Sig: Dry the area and apply a small amount 3-4x/day. Do not eat or drink for one hour after application

Rx Amlexanox oral paste 5% (Aphthasol) Disp: 5 gm Sig: Apply to affected area qid Benign Pemphigoid

• “Cicatricial Pemphigoid” • Chronic, autoimmune disease • 3x as common as • Average age 50-60, 2x more common in females • Oral, ocular, and genital mucosa ± others • Gingiva ()

(Scully et al 1999 )(Bagan et al 2005) Benign Mucous Membrane Pemphigoid

• to hemidesmosomes • Is a family of diseases, different antigens • BP 180, BP 230, laminin-5, etc • Separation of the epithelium from the CT • + Nikolsky’s sign Benign Mucous Membrane Pemphigoid (BCD, July 2010) Based on 199 patients –72.4% Female average age 59.6

–27.6% Male average age 63.8

–Combined average age 60.8 Benign Mucous Membrane Pemphigoid (BCD, July 2010) Clinical sites • Gingiva 96% • Gingiva only 67.2% • Buccal Mucosa 18.7% • Gingiva + buccal mucosa mucosa 16.5% • Palate 10.1% • Gingiva + palate 9.6% • Tongue 4.5% • Gingiva + tongue 4.5% • 1.1% • Gingiva + pharynx 1.1% Benign Mucous Membrane Pemphigoid • Diagnosis – Histologic appearance: • Subepithelial split with separation at the • Non-specific – Direct Immunofluorescence • IgG and/or C3 at basement membrane zone • Occasionally IgA, IgM Benign Mucous Membrane Pemphigoid • Treatment – Referral to an ophthalmologist – Topical corticosteroids – Good measures can help to decrease severity – Carrier trays – Dapsone – Tetracycline or and niacinamide – Systemic corticosteroids – Systemic corticosteroids + Cyclophosphamide – Intravenous (IV) human immunoglobulin Benign Mucous Membrane Pemphigoid • Highest Potency Topical Corticosteroid Rx Clobetasol 0.05% gel (Temovate) Disp: 15 gram tube Sig: Dry the area and apply a small amount 3-4x/day. Do not eat or drink for one hour after application. • Systemic Corticosteroid Rx Prednisone 10 mg tablet Disp: 40 tabs Sig: Two tabs bid x 7 days, then 1 tab bid X 4 days, the 1 tab daily until gone Oral Allergic Reactions Types of Allergic Reactions (BCD, January 2004)

• Cinnamon/Toothpaste/Preservatives 59 • Drug Lichenoid 53 • Dental Restorative Materials 45 • Non specific 11 Allergic

• Acute – Burning, erythema

• Chronic – Erythematous or white Oral Allergic Reactions

• Clinical: – Involvement of cheek and tongue on same side – Gingival desquamation Toothpaste

• Signs of Dentifrice Allergy

– Generalized or localized gingivitis (desquamative gingivitis) – Mucositis/glossitis – Cheilitis – – Perioral Toothpaste Hypersensitivity

• Flavoring agents as sensitizers: – Cinnamon oil – Cinnamic aldehyde – Menthol (also in pepermint) – Mint/Spearmint – (from eucalyptus oil) – Essential oils – L-carvone – Anethole Xerostomia

• Subjective sensation of a dry mouth • Common problem and in 25% of older adults • Multiple causes • Complications: – Candidiasis – Prone to cervical and root caries – Alteration of taste Common Causes for Xerostomia

• Medications • Caffeine/ • Smoking • Radiation therapy to head and neck • Sjögren’s syndrome • Primary Biliary cirrhosis • Diabetes mellitus • Sarcoidosis • of salivary glands Diagnosis of Xerostomia

• A positive response to any of the following questions has been associated with reduced : – Does the amount of saliva in your mouth seem to be too little? – Does your mouth feel dry when eating a meal? – Do you sip liquids to aid in swallowing dry food? – Do you have difficulty swallowing?

(Plemons et al 2014) Clinical of Xerostomia • Teeth – Increased incidence of (cervical and incisal) – Enamel demineralization (chalky spots at the cervical regions of the teeth) – Increased plaque accumulation – Enamel erosion and – Increased tooth hypersensitivity

(Plemons et al 2014) Clinical Signs and Symptoms of Xerostomia • Oral mucosa: – Mucositis – Mucosal desquamation – Atrophic mucosa – Allergic or contact stomatitis and lichenoid lesions (mostly opposing metal restoration) – Recurrent – Traumatic ulcerations on the lateral border of the tongue and buccal mucosa – Painful or burning mouth

(Plemons et al 2014) Clinical Signs and Symptoms of Xerostomia • Tongue – Dryness, fissuring, lobulation – – Erythema – Loss of papillae – Crenations on tongue (scalloped borders) Clinical Signs and Symptoms of Xerostomia • Lips – Dryness, chapping – Peeling – Fissuring – Clinical Signs and Symptoms of Xerostomia • Major salivary glands – Poor salivary output – Frothy saliva – Absent or reduced salivary pooling – Swelling and enlargement of salivary glands – Recurrent affecting major salivary glands Clinical Signs and Symptoms of Xerostomia • Oral cavity – Oral allergic or contact reactions – Halitosis – Difficulty talking, chewing or swallowing – Plaque accumulation – Altered taste – Food retention and debris on the teeth or tongue or along gingival margins • Other – Dry eye accompanied by dry mouth (Sjogren syndrome) Management of Xerostomia • Patient education – Meticulous oral hygiene regimen – Elimination of alcohol, smoking, caffeine consumption – Maintaining adequate hydration • Management of systemic conditions and medication use in consultation with patient’s physician/oncologist • Salivary stimulants (sialagogues): pilocarpine (Salagen), cevimeline (Evoxac) Management of Xerostomia

• Sugarless candies, gum • Oral lubricants (, gels, spray) • Candidiasis prevention and control • Patients with dry mouth, dry eyes and enlargement should be evaluated for Sjogren’s syndrome – 16-fold increased risk of developing Management of Xerostomia

• Oral lubricants – Xylimelts – Dentiva – Salese – Oramoist • Sialagogues: Rx Pilocarpine (Salagen) 5 mg tablets Disp: 120 tablets Sig: one tablet PO qid

Rx Cevimeline (Evoxac) 30 mg capsules Disp: 90 capsules Sig: one capsule PO tid

Geographic tongue

• “” • “Benign migratory glossitis” • Common • Unknown etiology • Clinical – 2/3 females – Dorsal and lateral tongue – Depapillated erythematous patch surrounded by a yellow-white border – Heal spontaneously and recur at different site – Often associated with Geographic tongue

• Treatment: Only for symptomatic patients – Topical corticosteroids Rx Fluocinonide gel or cream 0.05% (Lidex) Disp: 15 or 30 gram tube Sig: Dry the area and apply a small amount 3-4x/day. Do not eat or drink for one hour after application Rx Clobetasol 0.05% gel (Temovate) Disp: 15 gram tube Sig: Dry the area and apply a small amount 3-4x/day. Do not eat or drink for one hour after application.

– Zinc supplement: 220 mg daily Pharmacologic Therapy for Common Oral Mucosal Conditions Anti-inflammatory/Immunosuppressants

• High Potency Topical Corticosteroids – Fluocinonide 0.05% (Lidex) – 0.20% (Synalar HP) – Acetonide 0.5% (Aristocort Kenalog) • Kenalog in orabase 0.1% – 0.25% (Topicort) Anti-inflammatory/Immunosuppressants

• Highest Potency Topical Steroids – 0.05% (Temovate) – dipropionate 0.05% (Diprolene) – Halobetasol propionate ointment 0.05% (Ultravate) Anti-inflammatory/Immunosuppressants

Rx Fluocinonide gel or cream 0.05% (Lidex) Disp: 15 or 30 gram tube Sig: Dry the area and apply a small amount 3-4x/day. Do not eat or drink for one hour after application.

Rx Bethametasone dipropionate gel 0.05% Disp: 15 gm Sig: Apply sparingly to affected areas bid

Rx Decadron Elixir 0.5mg/5ml Disp: two 100 ml bottles Sig: Rinse with 1 tsp for 3-4 min and expectorate after meals and at bedtime Anti-inflammatory/Immunosuppressants Rx Clobetasol 0.05% gel (Temovate) Disp: 15 gram tube Sig: Dry the area and apply a small amount 3-4x/day. Do not eat or drink for one hour after application.

Rx Prednisone 10 mg tablet Disp: 40 tabs Sig: Two tabs bid x 7 days, then 1 tab bid X 4 days, the 1 tab daily until gone

Rx Amlexanox oral paste 5% (Aphthasol) Disp: 5 gm Sig: Apply to affected area qid

• Topical antifungal therapy Rx: Nystatin (Mycostatin, Nilstat) oral suspension 100,000 U/mL Disp: 240 ml Sig: Rinse with 1 tsp. qid for 3 min by the clock. Expectorate.

Clotrimazole (Mycelex) Troche 10 mg Disp: 70 Sig: Dissolve one troche slowly in mouth 5Xs daily for 14 days. Antifungals • Systemic antifungal therapy Rx: Fluconazole (Diflucan) tablets 100 mg Disp: 15 tablets Sig: Take 2 tablets on day 1, then 1 tablet daily Antifungals

• Angular cheilitis Rx: Ketoconazole (Nizoral) crm 2% Disp: 15 g tube Sig: Apply sparingly to corners of mouth after meals and before bed

Nystatin & ointment (Mycolog II, Mytrex) ointment Disp: 15 g tube Sig: Apply to affected sites after meals and before bed

Polymyxin B/Bacitracin (Polysporin) ointment (OTC) Disp: 15 g tube Sig: Apply to affected sites after meals and before bed. Antifungals

• Treatment of dentures in patients with Candidiasis • Reinfection can occur if denture is not also treated • Options include soaking denture in 1:10 solution of sodium hypochlorite & water overnight 3 times during treatment Antivirals

• Primary Herpes – Systemic antiviral therapy Rx: Acyclovir capsules 200 mg Disp: 42 capsules Sig: Take 2 capsules 3 times a day

Rx: Valacyclovir HCL (Valtrex) 1000 mg or Famciclovir (Famvir) 500 mg Disp: 14 caps Sig: Take I caplet twice a day Antivirals

• Recurrent Herpes – Treat during prodromal symptoms • Topical antiviral therapy Rx: Penciclovir cream 1% Disp: 1 tube Sig: Apply to area every 2 hours for 4 days, beginning with first symptoms Antivirals

• Recurrent Herpes – Treat during prodromal symptoms • Systemic antiviral therapy Rx: Valacyclovir HCL (Valtrex) 1000 mg Disp: 4 caplets Sig: Take 2 caplets at first sign of a cold sore, then 2 caplets 12 hours later

Rx: Famciclovir (Famvir) 500 mg Disp: 3 tablets Sig: Take 3 tablets as a single dose Symptomatic Relief

Rx Mix Dimetapp Elixir 40 ml Kaopectate 80 ml Distilled water 120 ml Sig: Rinse with 1 tsp and expectorate as needed Symptomatic Relief Rx in Orabase OTC* Rx Xylocaine Viscous 2%* Disp: 100 ml Sig: Rinse with 1 tsp as needed and expectorate

*Attention: Vicous and topical benzocaine should be avoided in pediatric patients because of reports of lidocaine-induced seizures in children and an association between topical benzocaine and methemoglobinemia. References

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• Fang M, Zhang W, Chen Y, He Z. Malignant transformation of oral lichen planus: a retrospective study of 23 cases. Quintessence Int 2009;40(3):235-42. • Gandolfo S, Richiardi L, Carrozzo M, BroccolettiR, Carbone M, Pagano M, et al. Risk of oral squamous cell carcinoma in 402 patients with oral lichen planus: a follow-up study in an Italian population. Oral Oncol 2004;40(1):77-83. • van der Meij EH, Schepman KP, Smeele LE, van der Wal JE, Bezemer PD, van der Waal I. A review of the recent literature regarding malignant transformation of oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88(3):307-10. • Miller RL et al. Oral Surg Oral Med Oral Pathol 1992; 73:708-716. • Allen CM and Blozis GG. J Am Dent Assoc 1988; 115:664-667. • Issa Y et al. Br. Dent J. 2005;198:361-366. • Moller H. 2002;47:63-66. • Scully C et al. Update on mucous membrane pemphigoid. Oral Surg Oral Med Oral Pathol 1999; 88:56-68. • Bagan J et al. Number III mucous membrane pemphigoid. Oral Dis 2005;11:197-218